ORCID Profile
0000-0001-9130-4592
Current Organisation
University of South Florida
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Publisher: Wiley
Date: 07-2009
DOI: 10.1002/CNE.21949
Abstract: Sanfilippo syndrome type B (MPS III B) is caused by a deficiency of alpha-N-acetylglucosaminidase enzyme (Naglu), leading to accumulation of heparan sulfate (HS), a glycosaminoglycan (GAG), within lysosomes and to eventual progressive cerebral and systemic multiple organ abnormalities. Treatment of MPS patients is mainly supportive and enzyme replacement cell therapy shows promise for treating this disease. One new approach for potential treatment of MPS III B is human umbilical cord blood (hUCB) cell transplantation. Recently, we demonstrated that administration of hUCB cells into the cerebral ventricle of presymptomatic Naglu mice had a beneficial effect, probably due to enzyme delivery into the enzyme-deficient mutant mice. However, administration of these cells into the systemic circulation of mutant mice could be more advantageous and may lead to new strategies of enzyme replacement for Sanfilippo. The aim of this study was to determine the effect of intravenous administration of hUCB cells into a mouse model of Sanfilippo Syndrome type B. The major findings in our study were that hUCB cell administration improved behavioral outcomes (decreased hyper/stereotypical activity and improved cognitive function). Cells widely distribute within and outside the CNS and intraparenchymally migrate. Administered cells have an antiinflammatory effect (Th2-associated cytokines) in the brain and reduce heparan sulfate accumulation in the liver and spleen. Our results demonstrate the advantages of intravenously administering hUCB cells into a mouse model of Sanfilippo Syndrome type B, the advantages probably a result of Naglu delivery to enzyme-deficient organs.
Publisher: Future Medicine Ltd
Date: 07-2014
DOI: 10.2217/RME.14.32
Publisher: Elsevier BV
Date: 03-2009
Publisher: Hindawi Limited
Date: 2010
DOI: 10.1100/TSW.2010.39
Abstract: The annual meeting of the American Society for Neural Therapy and Repair (ASNTR) has always introduced us to top-notch and up-to-date approaches for regenerative medicine related to neuroscience, ranging from stem cell–based therapy to novel drugs. The 16th ASNTR meeting focused on a variety of different topics, including the unknown pathogenesis or mechanisms of specific neurodegenerative diseases, stem cell biology, and development of novel alternative medicines or devices. Newly developed stem cells, such as amniotic epithelial stem cells and induced pluripotent stem cells, as well as well-known traditional stem cells, such as neural, embryonic, bone marrow mesenchymal, and human umbilical cord blood–derived stem cells, were reported. A number of commercialized stem cells were also covered at this meeting. Fetal neural tissues, such as ventral mesencephalon, striatum, and Schwann cells, were investigated for neurodegenerative diseases or spinal cord injury. A number of studies focused on novel methods for drug monitoring or graft tracking, and combination therapy with stem cells and medicine, such as cytokines or trophic factors. Finally, the National Institutes of Health guidelines for human stem cell research, clinical trials of commercialized stem cells without larger animal testing, and prohibition of medical tourism were big controversial issues that led to heated discussion.
Publisher: Informa UK Limited
Date: 15-07-2016
Publisher: SAGE Publications
Date: 08-2019
Abstract: Rodents display “empathy” defined as perceived physical pain or psychological stress by cagemates when co-experiencing socially distinct traumatic events. The present study tested the hypothesis that empathy occurs in adult rats subjected to an experimental neurological disorder, by allowing co-experience of stroke with cagemates. Psychological stress was measured by general locomotor activity, Rat Grimace Scale (RGS), and plasma corticosterone. Physiological correlates were measured by Western blot analysis of advanced glycation endproducts (AGE)-related proteins in the thymus. General locomotor activity was impaired in stroke animals and in non-stroke rats housed with stroke rats suggesting transfer of behavioral manifestation of psychological stress from an injured animal to a non-injured animal leading to social inhibition. RGS was higher in stroke rats regardless of social settings. Plasma corticosterone levels at day 3 after stroke were significantly higher in stroke animals housed with stroke rats, but not with non-stroke rats, indicating that empathy upregulated physiological stress level. The expression of five proteins related to AGE in the thymus reflected the observed pattern of general locomotor activity, RGS, and plasma corticosterone levels. These results indicate that stroke-induced psychological stress manifested on both the behavioral and physiological levels and appeared to be affected by empathy-associated social settings.
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.BRAINRES.2009.05.040
Abstract: Recent laboratory evidence implicates matrix metalloproteinases (MMPs) as playing a pivotal role in ischemic and traumatic brain injuries (TBI). Here, quantitative real-time PCR analyses revealed that brains from TBI rats displayed significantly elevated MMP-9 expression at 24 h post-TBI, which remained upregulated at least until 48 h after injury. Immunohistochemical analyses similarly revealed significantly increased MMP-9 immunoreactivity at 24 and 48 h post-TBI. These results demonstrate that alterations in MMPs (i.e., MMP-9) commenced immediately after TBI, suggesting that treatment strategies designed to maintain MMP integrity should be initiated in the acute phase of injury.
Publisher: Springer Science and Business Media LLC
Date: 13-04-2017
DOI: 10.1038/S41598-017-00993-0
Abstract: Vascular pathology, including blood-CNS barrier (B-CNS-B) damage via endothelial cell (EC) degeneration, is a recently recognized hallmark of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. B-CNS-B repair may be a new therapeutic approach for ALS. This study aimed to determine effects of transplanted unmodified human bone marrow CD34+ (hBM34+) cells into symptomatic G93A mice towards blood-spinal cord barrier (BSCB) repair. Thirteen weeks old G93A mice intravenously received one of three different doses of hBM34+ cells. Cell-treated, media-treated, and control mice were euthanized at 17 weeks of age. Immunohistochemical (anti-human vWF, CD45, GFAP, and Iba-1) and motor neuron histological analyses were performed in cervical and lumbar spinal cords. EB levels in spinal cord parenchyma determined capillary permeability. Transplanted hBM34+ cells improved behavioral disease outcomes and enhanced motor neuron survival, mainly in high-cell-dose mice. Transplanted cells differentiated into ECs and engrafted within numerous capillaries. Reduced astrogliosis, microgliosis, and enhanced perivascular end-feet astrocytes were also determined in spinal cords, mostly in high-cell-dose mice. These mice also showed significantly decreased parenchymal EB levels. EC differentiation, capillary engraftment, reduced capillary permeability, and re-established perivascular end-feet astrocytes in symptomatic ALS mice may represent BSCB repair processes, supporting hBM34+ cell transplantation as a future therapeutic strategy for ALS patients.
Publisher: Elsevier BV
Date: 05-2009
Publisher: Elsevier BV
Date: 12-2019
Publisher: SAGE Publications
Date: 11-06-2019
Abstract: The therapeutic application of human umbilical cord blood cells has been an area of great interest for at least the last 25 years. Currently, cord blood cells are approved for reconstitution of the bone marrow following myeloablation in both young and old patients with myeloid malignancies and other blood cancers. Translational studies investigating alternative uses of cord blood have also shown that these cells not only stimulate neurogenesis in the aged brain but are also potentially therapeutic in the treatment of adult neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer’s disease, ischemic stroke, traumatic brain injury, and Parkinson’s disease. Recent advances in the clinical application of cord blood cells by Dr. Joanne Kurtzberg and colleagues have found that non-HLA matched allogeneic banked cord blood units in immunocompetent patients with ischemic stroke are safe and well tolerated. Although the exact mechanism(s) of action that provide the beneficial effects observed from a cord blood cell-based therapy are currently unknown, several studies using models of neurodegenerative disease have shown these cells are immune-modulatory and anti-inflammatory. Thus, any future clinical studies investigating the efficacy of this cord blood cell therapeutic would strongly benefit from the inclusion of methodologies to determine changes in both markers of inflammation and the response of immune tissues, such as the spleen, in subjects receiving cell infusion.
Publisher: Informa UK Limited
Date: 05-2008
Publisher: SAGE Publications
Date: 05-2016
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of motor neurons in the spinal cord and brain. This disease clinically manifests as gradual muscular weakness and atrophy leading to paralysis and death by respiratory failure. While multiple interdependent factors may contribute to the pathogenesis of ALS, increasing evidence shows the possible presence of autoimmune mechanisms that promote disease progression. The potential use of plasma derived from human umbilical cord blood (hUCB) as a therapeutic tool is currently in its infancy. The hUCB plasma is rich in cytokines and growth factors that are required for growth and survival of cells during hematopoiesis. In this study, we investigated the effects of hUCB plasma on the mitogen-induced proliferation of mononuclear cells (MNCs) isolated from the peripheral blood of ALS patients and apoptotic activity by detection of caspase 3/7 expression of the isolated MNCs in vitro. Three distinct responses to phytohemagglutinin (PHA)-induced proliferation of MNCs were observed, which were independent of age, disease duration, and the ALS rating scale: Group I responded normally to PHA, Group II showed no response to PHA, while Group III showed a hyperactive response to PHA. hUCB plasma attenuated the hyperactive response (Group III) and potentiated the normal response in Group I ALS patients, but did not alter that of the nonresponders to PHA (Group II). The elevated activity of caspase 3/7 observed in the MNCs from ALS patients was significantly reduced by hUCB plasma treatment. Thus, study results showing different cell responses to mitogen suggest alteration in lymphocyte functionality in ALS patients that may be a sign of immune deficiency in the nonresponders and autoimmunity alterations in the hyperactive responders. The ability of hUCB plasma to modulate the mitogen cell response and reduce caspase activity suggests that the use of hUCB plasma alone, or with stem cells, may prove useful as a therapeutic in ALS patients.
Publisher: Humana Press
Date: 2008
DOI: 10.1007/978-1-59745-133-8_30
Abstract: Stem cell transplantation to replace damaged tissue or correct metabolic disease holds the promise of helping a myriad of human afflictions. Although a great deal of attention has focused on pluripotent stem cells derived from embryos, adult stem cells have been described in a variety of tissues, and they likely will prove to be as beneficial as embryonic stem cells in cell replacement therapy and control of inbred errors of metabolism. We describe methods by which stem cells can be introduced into the nervous system, although the techniques are applicable to any portion of the body to be targeted or any cell that may be used for cell therapy. The first and most straight-forward method is introduction of stem cells directly into the brain parenchyma. The second, which in our hands has proven to be superior in some instances, is introduction of the stem cells into the circulatory system.
Publisher: Mary Ann Liebert Inc
Date: 06-2009
Abstract: Current treatments of neurological disorders such as Parkinson's disease and stroke are only partially effective. Consequently new therapies such as cell transplantation are of great interest. Cell therapy has shown promising results in animal models and in limited clinical trials. This form of treatment does have its own concerns, such as what factors control the survival and/or migration of the transplanted cells and how do they exert their benefit. Recent studies on tracking the transplants, such as prelabeling of the cells prior to transplant, and those elucidating the role of chemokines, as well as microglial and inflammatory responses, that may initiate the movement and survival of these cells are discussed in this review. A better understanding of these mechanism-driven pathways of neural repair will facilitate the clinical application of cell therapy for neurological disorders.
Publisher: SAGE Publications
Date: 08-05-2019
Abstract: Our group previously demonstrated that administration of a CD34-negative fraction of human non- hematopoietic umbilical cord blood stem cells (UCBSC) 48 h after ischemic injury could reduce infarct volume by 50% as well as significantly ameliorate neurological deficits. In the present study, we explored possible mechanisms of action using next generation RNA sequencing to analyze the brain transcriptome profiles in rats with ischemic brain injury following UCBSC therapy. Two days after ischemic injury, rats were treated with UCBSC. Five days after administration, total brain mRNA was then extracted for RNAseq analysis using Illumina Hiseq 2000. We found 275 genes that were significantly differentially expressed after ischemic injury compared with control brains. Following UCBSC treatment, 220 of the 275 differentially expressed genes returned to normal levels. Detailed analysis of these altered transcripts revealed that the vast majority were associated with activation of the immune system following cerebral ischemia which were normalized following UCBSC therapy. Major alterations in gene expression profiles after ischemia include blood-brain-barrier breakdown, cytokine production, and immune cell infiltration. These results suggest that UCBSC protect the brain following ischemic injury by down regulating the aberrant activation of innate and adaptive immune responses.
Publisher: Springer Science and Business Media LLC
Date: 08-06-2010
DOI: 10.1007/S12015-010-9163-0
Abstract: Spinal cord injury (SCI) develops primary and secondary damage to neural tissue and this often results in permanent disability of the motor and sensory functions. However, there is currently no effective treatment except methylprednisolone, and the use of methylprednisolone has also been questioned due to its moderate efficacy and the drug's downside. Regenerative medicine has remarkably developed since the discovery of stem cells, and many studies have suggested the potential of cell-based therapies for neural injury. Especially, the therapeutic potential of human umbilical cord blood cells (hUCB cells) for intractable neurological disorders has been demonstrated using in vitro and vivo models. The hUCB cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Their ability to produce several neurotropic factors and to modulate immune and inflammatory reactions has also been noted. Recent evidence has emerged suggesting alternative pathways of graft-mediated neural repair that involve neurotrophic effects. These effects are caused by the release of various growth factors that promote cell survival, angiogenesis and anti-inflammation, and this is all aside from a cell replacement mechanism. In this review, we present the recent findings on the stemness properties and the therapeutic potential of hUCB as a safe, feasible and effective cellular source for transplantation in SCI. These multifaceted protective and restorative effects from hUCB grafts may be interdependent and they act in harmony to promote therapeutic benefits for SCI. Nevertheless, clinical studies with hUCB are still rare because of the concerns about safety and efficiency. Among these concerns, the major histocompatibility in allogeneic transplantation is an important issue to be addressed in future clinical trials for treating SCI.
Publisher: Elsevier
Date: 2007
Publisher: SAGE Publications
Date: 30-06-2017
Publisher: Elsevier BV
Date: 09-2007
Publisher: Bentham Science Publishers Ltd.
Date: 26-04-2012
Publisher: Wiley
Date: 19-10-2016
DOI: 10.1002/JCP.25629
Publisher: SAGE Publications
Date: 2012
Abstract: Neurorestoratology is a newborn and emerging distinct discipline in the neuroscience family. Its establishment will definitely speed up the advance of this promising frontier realm. A worldwide association for Neurorestoratology and several official journals covering this discipline have recently been set up. Clinical practice has demonstrated that the sequelae of damages and diseases of the CNS can be functionally restored to some degree. Obstacles that hinder the promising methods of Neurorestoratology to be translated from the bench to the bedside include political, governmental, religious, ethical, economic, and scientific factors or in most instances they work in combination. Falsehoods against the recognition of neurorestoratology include: 1) no therapeutic method is currently available that suggests that it is possible to repair, even partially, neurological functions 2) according to the media, a cure will be very soon found for patients with severe spinal cord injury, brain trauma, and progressively deteriorated CNS degenerative diseases 3) randomizing double blind control designed studies are the only gold standard for clinical study self-comparison designed studies should be ignored and neglected. Future directions for neurorestoratology include the comparison and integration of current and upcoming available neurorestoration methods to look for the optimization regimes, and edit and publish clinical neurorestoratology treatment guidelines.
Publisher: Impact Journals, LLC
Date: 31-01-2018
Publisher: MDPI AG
Date: 23-05-2019
DOI: 10.3390/F10050445
Abstract: This paper is focused on searching for the suitable discount rate to be applied to the valuation of a project related to forests in the USA, e.g., a recreational area inside a national park. To do this, we propose a new model based on hazard rate concepts, i.e., based on the risk that waiting time implies. More specifically, we derive the discount function whose instantaneous discount rate is the hazard rate of the system supporting the investment. We determine the rate of failure corresponding to different partition criteria of the whole system in our case, we can use the information on forest fires caused in different ways, in different states or in different types of forest surfaces. After showing independence between the forest fires by states and causes, we derive a specific discount function for each cause which can be applied to every state or set of states which agree to fight against a concrete cause of forest fire. Additionally, we obtain a unique discount function by weighting the partial discount functions by type of forest surfaces. Our results are in line with the recommendations from several authors about using decreasing discount rates for projects with very long-term impacts.
Publisher: Wiley
Date: 18-10-2018
DOI: 10.1111/JCMM.13898
Publisher: Bentham Science Publishers Ltd.
Date: 05-2008
DOI: 10.2174/156720208784310259
Abstract: Monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein (MIP-1alpha) are implicated in monocyte infiltration into the central nervous system (CNS) under pathological conditions. We previously showed that in vivo human umbilical cord blood cells (HUCB) migrate toward brain injury after middle cerebral artery occlusion (MCAO). We hypothesized that MCP-1 and MIP-1alpha may participate in the recruitment of HUCB towards the injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO), and 24 hours later the production of MCP-1 and MIP-1alpha in the brain was examined with immunohistochemistry, ELISA, and western blotting. The chemotactic effect of MCP-1 and MIP-1alpha, and the expression of MCP-1 receptor CCR2 and MIP-1alpha receptor CCR1, CCR5 on the surface of HUCB were also examined. MCP-1 and MIP-1alpha expression were significantly increased in the ischemic hemisphere of brain, and significantly promoted HUCB cell migration compared to the contralateral side. This cell migration was neutralized with polyclonal antibodies against MCP-1 or MIP-1alpha. Also chemokine receptors were constitutively expressed on the surface of HUCB cells. The data suggested that the increased chemokines in the ischemic area can bind cell surface receptors on HUCB, and induce cell infiltration of systemically delivered HUCB cells into the CNS in vivo.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2013
Publisher: Proceedings of the National Academy of Sciences
Date: 17-07-2007
Publisher: Public Library of Science (PLoS)
Date: 21-11-2007
Publisher: SAGE Publications
Date: 2013
Abstract: Cell transplantation is a potentially powerful approach for the alleviation of chronic pain. The strategy of cell transplantation for the treatment of pain is focused on cell-based analgesia and neural repair. ( 1 ) Adrenal medullary chromaffin cells and the PC12 cell line have been used to treat cancer pain and neuropathic pain in both animal models and human cases. As biological or living minipumps, these cells produce and secrete pain-reducing neuroactive substances if administered directly into the spinal subarachnoid space. ( 2 ) Cell implantation for pain neurorestorative therapy is a new concept and an emerging research field for pain control along with neural repair. Possible neurorestorative mechanisms include neuroprotective, neurotrophic, neuroreparative, neuroregenerative, neuromodulation, or neuroconstructive interventions, as well as immunomodulation and enhancing the microcirculation. These factors may ultimately restore the damaged or irritated condition of the lesioned nerves. The growing preclinical and clinical data show that neural stem rogenitor cells, olfactory ensheathing cells, mesenchymal stromal cells, and CD34 + cells have the capacity to manage intractable pain and improve neurological functions. Cell delivery routes include local, intrathecal, or intravascular implants. Although these strategies are still in their infancy phase for pain neurorestoratology, cell-based therapies could open up new avenues for the relief of pain. In this review, these aspects are critically analyzed based on our own investigations. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.
Publisher: SAGE Publications
Date: 09-2009
Abstract: Irreversible and permanent damage develop immediately adjacent to the region of reduced cerebral blood perfusion in stroke patients. Currently, the proven thrombolytic treatment for stroke, tissue plasminogen activator, is only effective when administered within 3 h after stroke. These disease characteristics should be taken under consideration in developing any therapeutic intervention designed to widen the narrow therapeutic range, especially cell-based therapy. Over the past several years, our group and others have characterized the therapeutic potential of human umbilical cord blood cells for stroke and other neurological disorders using in vitro and vivo models focusing on the cells' ability to differentiate into nonhematopoietic cells including neural lineage, as well as their ability to produce several neurotrophic factors and modulate immune and inflammatory reaction. Rather than the conventional cell replacement mechanism, we advance alternative pathways of graft-mediated brain repair involving neurotrophic effects resulting from release of various growth factors that afford cell survival, angiogenesis, and anti-inflammation. Eventually, these multiple protective and restorative effects from umbilical cord blood cell grafts may be interdependent and act in harmony in promoting therapeutic benefits for stroke.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.BRAINRES.2012.05.056
Abstract: Vascular pathology, including blood-brain/spinal cord barrier (BBB/BSCB) alterations, has recently been recognized as a key factor possibly aggravating motor neuron damage, identifying a neurovascular disease signature for ALS. However, BBB/BSCB competence in sporadic ALS (SALS) is still undetermined. In this study, BBB/BSCB integrity in postmortem gray and white matter of medulla and spinal cord tissue from SALS patients and controls was investigated. Major findings include (1) endothelial cell damage and pericyte degeneration, (2) severe intra- and extracellular edema, (3) reduced CD31 and CD105 expressions in endothelium, (4) significant accumulation of perivascular collagen IV, and fibrin deposits (5) significantly increased microvascular density in lumbar spinal cord, (6) IgG microvascular leakage, (7) reduced tight junction and adhesion protein expressions. Microvascular barrier abnormalities determined in gray and white matter of the medulla, cervical, and lumbar spinal cord of SALS patients are novel findings. Pervasive barrier damage discovered in ALS may have implications for disease pathogenesis and progression, as well as for uncovering novel therapeutic targets.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2019
DOI: 10.1038/S41598-019-41747-4
Abstract: Convincing evidence demonstrated impairment of the blood-spinal cord barrier (BSCB) in Amyotrophic Lateral Sclerosis (ALS), mainly by endothelial cell (EC) alterations. Replacing damaged ECs by cell transplantation is a potential barrier repair strategy. Recently, we showed that intravenous (iv) administration of human bone marrow CD34 + (hBM34 + ) cells into symptomatic ALS mice benefits BSCB restoration and postpones disease progression. However, delayed effect on motor function and some severely damaged capillaries were noted. We hypothesized that hematopoietic cells from a restricted lineage would be more effective. This study aimed to establish the effects of human bone marrow-derived endothelial progenitor cells (hBMEPCs) systemically transplanted into G93A mice at symptomatic disease stage. Results showed that transplanted hBMEPCs significantly improved behavioral disease outcomes, engrafted widely into capillaries of the gray/white matter spinal cord and brain motor cortex/brainstem, substantially restored capillary ultrastructure, significantly decreased EB extravasation into spinal cord parenchyma, meaningfully re-established perivascular astrocyte end-feet, and enhanced spinal cord motor neuron survival. These results provide novel evidence that transplantation of hBMEPCs effectively repairs the BSCB, potentially preventing entry of detrimental peripheral factors, including immune/inflammatory cells, which contribute to motor neuron dysfunction. Transplanting EC progenitor cells may be a promising strategy for barrier repair therapy in this disease.
Publisher: SAGE Publications
Date: 08-2006
DOI: 10.3727/000000006783981611
Abstract: We are investigating the effects of human umbilical cord blood mononuclear progenitor cells (HUCBC) for the treatment of acute myocardial infarction because human cord blood is a readily available and an abundant source of primitive cells that may be beneficial in myocardial repair. However, there is currently no scientific consensus on precisely when to inject stem rogenitor cells for the optimal treatment of acute myocardial infarction. We used an in vitro assay to determine the attraction of infarcted rat myocardium at 1, 2, 2.5, 3, 6, 12, 24, 48, and 96 h after left anterior descending coronary artery (LAD) occlusion from 45 rats for HUCBC in order to determine the optimal time to transplant HUCBC after myocardial infarction. Our assay is based on the migration of fluorescent DAPI-labeled HUCBC from wells in an upper chamber of a modified Boyden apparatus through a semiporous polycarbonate membrane into wells in a lower chamber that contain either normal or infarcted myocardium. DAPI-labeled HUCBC (100,000) were placed in each of the separate wells above the membrane that corresponded to normal or infarct homogenate in the lower wells. The greatest HUCBC migration to infarcted myocardium occurred at 2 h and 24 h after LAD occlusion in comparison with normal controls. A total of 76,331 ± 3384 HUCBC migrated to infarcted myocardium at 2 h and 69,911 ±2732 at 24 h after LAD occlusion (both p 0.001) and significantly exceeded HUCBC migration to normal heart homogenate. The HUCBC migration remained greatest at 2 and 24 h after LAD occlusion when the number of migrated cells was adjusted for the size of each myocardial infarction. Injection of 106 HUCBC in saline into infarcted myocardium of non immunosuppressed rats within 2 h (n = 10) or at 24 h (n = 5) after LAD occlusion resulted in infarction sizes 1 month later of 6.4 ± 0.01% and 8.4 ± 0.02% of the total left ventricular muscle area, respectively, in comparison with infarction sizes of 24.5 ± 0.02% (n = 10) in infarcted rat hearts treated with only saline (p 0.005). Acute myocardial infarction in rats treated with only saline increased the myocardial concentration of tumor necrosis factor-α (TNF-α) from 6.9 ± 0.8% to 51.3 ± 4.6%, monocyte/macrophage chemoattractant protein (MCP-1) from 10.5 ± 1.1% to 39.2 ± 2.0%, monocyte inflammatory protein (MIP) from 10.6± 1.6% to 23.1 ± 1.5%, and interferon-? (INF-?) from 8.9 ± 0.3% to 25.0 ± 1.7% between 2 and 12 h after coronary occlusion in comparison with known controls (all p 0.001). In contrast, the myocardial concentrations of these cytokines in rat hearts treated with HUCBC did not significantly change from the controls at 2, 6, 12, and 24 h after coronary occlusion. The present investigations suggest that infarcted myocardium significantly attracts HUCBC, that HUCBC can substantially reduce myocardial infarction size, and that HUCBC can limit the expression of TNF-α, MCP-1, MIP, and INF-? in acutely infarcted myocardium.
Publisher: Akademiai Kiado Zrt.
Date: 06-2012
Abstract: Cerebrovascular diseases are a major cause of death and long-term disability in developed countries. Tissue plasmin activator (tPA) is the only approved therapy for ischemic stroke, strongly limited by the short therapeutic window and hemorrhagic complications, therefore excluding most patients from its benefits. The rescue of the penumbra area of the ischemic infarct is decisive for functional recovery after stroke. Inflammation is a key feature in the penumbra area and it plays a dual role, improving injury in early phases but impairing neural survival at later stages. Stem cells can be opportunely used to modulate inflammation, abrogate cell death and, therefore, preserve neural function. We here discuss the possible role of stem cells derived from menstrual blood as restorative treatment for stroke. We highlight the availability, proliferative capacity, pluripotentiality and angiogenic features of these cells and explore their present and future experimental and clinical applications.
Publisher: Springer Science and Business Media LLC
Date: 09-2008
DOI: 10.1007/BF03033507
Publisher: Frontiers Media SA
Date: 19-10-2020
Publisher: Hindawi Limited
Date: 2011
DOI: 10.1100/2011/341532
Abstract: Insight into the expanding themes of regenerative medicine is provided by the American Society for Neural Therapy and Repair's annual meeting. The 17th meeting covered a wide range of neurodegenerative disorders, exploring methods to elucidate the currently unknown mechanisms behind the disorders, as well as possible treatments ranging from the use of growth factors, gene therapy to cell transplantation. The importance of growth factors, both as a contributing factor to a disease and as a possible treatment either solo, or as a consequence of, or in conjunction with, stem cell therapy, was highlighted. The potential for viral vectors was also explored either for cells prior to transplantation or as a direct treatment regime into the brain itself. Identification of biomarkers that would allow early detection of a disease is an important factor in our fight against disease. The ability to now perform whole genome analysis and biomolecular profiling provides hope that such markers could be identified which not only could identify this likely to suffer from a disorder but also could allow its progress to be monitored. A few preclinical and clinical cell transplantation trials were also introduced as potential areas of followup in the years to come.
Publisher: Springer Science and Business Media LLC
Date: 10-03-2020
DOI: 10.1007/S11357-020-00174-4
Abstract: Aging is associated with many pathophysiological changes that could lead to the onset of degenerative disease. Some of the physiological changes that occur with aging include increased inflammation and decreased stem cell proliferation, leading to decreased capacity for tissue regeneration and loss of function. In previous studies, we and others have found nutraceutical intervention to ameliorate some of the deleterious effects associated with aging. In particular, we have previously shown that NT-020, a supplement composed of a proprietary blend of blueberries, green tea, vitamin D3, and carnosine, is able to rescue age-related cognitive deficits, impaired neurogenesis, and inflammation in rats. We have also previously demonstrated that stem cells cultured with old serum showed decreased proliferation however, when stem cells were cultured in serum from old rats given a diet supplemented with NT-020, proliferation did not differ from that of cells cultured with serum from young rats. While it is clear that NT-020 is exerting a therapeutic, anti-aging effect, the mechanisms of action were yet to be fully elucidated.To that end, in the present study, we conducted a bioinformatics experiment to examine the rat proteome of serum from young and old control rats and young and old rats given a diet supplemented with NT-020. Serum from old rats showed an increase in some inflammatory and pro-aging factors while serum from old rats given a diet supplemented with NT-020 showed an increase in some anti-aging factors, most notably proteins associated with the complement system and autophagy. A number of immune functions that increase with age were shown to be downregulated with NT-020 treatment.
Publisher: Oxford University Press (OUP)
Date: 03-2012
DOI: 10.1093/BMB/LDS001
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/00207450701239442
Abstract: The spectrum and features of neurological disorders have been changed due to the Chernobyl catastrophe in the Republic of Belarus. More recently neurologists in Belarus have noted a significant increase in the frequency of myasthenia gravis (MG) with concomitant rise in the thymomas. There is some evidence suggesting that retroviruses play a key role in the development and pathogenesis of autoimmune diseases. This study analyzed thymomas from 45 MG patients from the Republic of Belarus by using PCR and primers for two regions of FV--gag and bel-2 genes. The results showed that none of the varied thymuses from the 45 MG patients contained FV genome. No relationship can be confirmed between FV and this disease and the results suggest that no pathological link between FV and MG exists.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2010
DOI: 10.1007/S12015-010-9174-X
Abstract: Cerebral ischemia induces death of all neural cell types within the region affected by the loss of blood flow. We have shown that administering human umbilical cord blood cells after a middle cerebral artery occlusion in rats significantly reduces infarct size, presumably by rescuing cells within the penumbra. In this study we examined whether the cord blood cells enhanced astrocyte survival in an in vitro model of hypoxia with reduced glucose availability. Primary astrocyte cultures were incubated for 2 h in no oxygen (95% N, 5% CO(2)) and low glucose (1% compared to 4.5%) media. Cord blood mononuclear cells were added to half the cultures at the beginning of hypoxia. Astrocyte viability was determined using fluorescein diacetate ropidium iodide (FDA/PI) labeling and cytokine production by the astrocytes measured using ELISA. In some studies, T cells, B cells or monocytes/macrophages isolated from the cord blood mononuclear fraction with magnetic antibody cell sorting (MACS) were used instead to determine which cellular component of the cord blood mononuclear fraction was responsible for the observed effects. Co-culturing mononuclear cord blood cells with astrocytes during hypoxia stimulated production of IL-6 and IL-10 during hypoxia. The cord blood T cells decreased survival of the astrocytes after hypoxia but had no effect on the examined cytokines. Our data demonstrate that the tested cord blood fractions do not enhance astrocyte survival when delivered in idually, suggesting there is either another cellular component that is neuroprotective or an interaction of all the cells is essential for protection.
Publisher: Springer Science and Business Media LLC
Date: 08-2012
Publisher: Springer Science and Business Media LLC
Date: 28-06-2015
Publisher: SAGE Publications
Date: 2020
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal disease of motor neuron degeneration in the brain and spinal cord. Progressive paralysis of the diaphragm and other respiratory muscles leading to respiratory dysfunction and failure is the most common cause of death in ALS patients. Respiratory impairment has also been shown in animal models of ALS. Vascular pathology is another recently recognized hallmark of ALS pathogenesis. Central nervous system (CNS) capillary damage is a shared disease element in ALS rodent models and ALS patients. Microvascular impairment outside of the CNS, such as in the lungs, may occur in ALS, triggering lung damage and affecting breathing function. Stem cell therapy is a promising treatment for ALS. However, this therapeutic strategy has primarily targeted rescue of degenerated motor neurons. We showed functional benefits from intravenous delivery of human bone marrow (hBM) stem cells on restoration of capillary integrity in the CNS of an superoxide dismutase 1 (SOD1) mouse model of ALS. Due to the widespread distribution of transplanted cells via this route, administered cells may enter the lungs and effectively restore microvasculature in this respiratory organ. Here, we provided preliminary evidence of the potential role of microvasculature dysfunction in prompting lung damage and treatment approaches for repair of respiratory function in ALS. Our initial studies showed proof-of-principle that microvascular damage in ALS mice results in lung petechiae at the late stage of disease and that systemic transplantation of mainly hBM-derived endothelial progenitor cells shows potential to promote lung restoration via re-established vascular integrity. Our new understanding of previously underexplored lung competence in this disease may facilitate therapy targeting restoration of respiratory function in ALS.
Publisher: American Scientific Publishers
Date: 05-2015
Publisher: Springer Science and Business Media LLC
Date: 26-09-2015
Publisher: SAGE Publications
Date: 2020
Abstract: Coronavirus disease 2019 or COVID-19 is highly infectious, which can lead to acute and chronic debilitating symptoms, as well as mortality. The advent of safe and effective vaccines or antiviral drugs remains distant in the future. Practical public health measures, such as social distancing, hand washing, and wearing a face mask, are the current recommended guidelines by the Centers for Disease Control and Prevention for limiting the spread of the virus. Weakened immune system and aberrant inflammation represent a major pathological symptom of COVID-19 patients. Based on the unique immunomodulatory properties of both convalescent plasma and stem cells, we discuss here their potential use for treating COVID-19.
Publisher: SAGE Publications
Date: 02-2011
Abstract: Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual blood-derived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.
Publisher: SAGE Publications
Date: 09-2013
Abstract: We have previously demonstrated in acute myocardial infarctions that human umbilical cord blood mononuclear cells (HUCBCs), which contain hematopoietic, endothelial, and mesenchymal stem cells, reduce acute myocardial infarction size by ≥50% and preserve LV contractility. We hypothesize that the beneficial effects of HUCBCs are due to secretion of biologically active factors that activate in cardiac endothelial cells and myocytes the cell survival protein Akt. We determined by protein microarrays the growth factors and anti-inflammatory cytokines secreted by HUCBCs into culture media during 12 h of hypoxia (1% O 2 ). We then determined by Western blots the effects of cell-free media from hypoxic-conditioned HUCBCs (HUCM) on activation of the cell survival protein Akt in human coronary artery endothelial cells and cardiac myocytes in culture during 24 h of 1% O 2 . We also determined in separate experiments endothelial cell and myocyte apoptosis by caspase-3 and Annexin V. In the present experiments, HUCBCs secreted multiple growth factors, anti-inflammatory cytokines, and inhibitors of metalloproteinase during normoxia and hypoxia. Human cord blood cells increased the concentration in culture media of angiopoietin, hepatocyte growth factor, interleukin-4, insulin-like growth factor, placental growth factor, vascular endothelial cell growth factor, angiogenin, and stem cell factor by 100 to ,000% during 12 h of 1% O 2 ( p 0.001). HUCM, which contained these biological factors, significantly increased Akt phosphorylation/activation in coronary artery endothelial cells and cardiac myocytes subjected to 24 h of 1% O 2 by more than 60% ( p 0.05) and increased the antiapoptotic protein Bcl-2 expression by 34–50% in comparison with endothelial cells and myocytes treated without HUCM in 1% O 2 ( p 0.05). HUCM also significantly decreased caspase-3 activity and decreased hypoxic endothelial cell and cardiac myocyte apoptosis by more than 40% in comparison with cells cultured without HUCM ( p 0.05). Inhibition of Akt activation in endothelial cells and myocytes by the sensitive and specific antagonist API-1 during 24 h of hypoxia nearly completely prevented the beneficial effects of HUCM on inhibiting caspase-3 activity and apoptosis. We conclude that HUCBCs secrete biologically active factors during hypoxia that activate survival proteins in endothelial cells and myocytes that significantly limit apoptosis.
Publisher: SAGE Publications
Date: 30-10-2018
Abstract: Stroke is a major cause of death and disability in the United States and around the world with limited therapeutic option. Here, we discuss the critical role of mitochondria in stem cell-mediated rescue of stroke brain by highlighting the concept that deleting the mitochondria from stem cells abolishes the cells’ regenerative potency. The application of innovative approaches entailing generation of mitochondria-voided stem cells as well as pharmacological inhibition of mitochondrial function may elucidate the mechanism underlying transfer of healthy mitochondria to ischemic cells, thereby providing key insights in the pathology and treatment of stroke and other brain disorders plagued with mitochondrial dysfunctions.
Publisher: Bentham Science Publishers Ltd.
Date: 05-2013
Publisher: Public Library of Science (PLoS)
Date: 03-01-2013
Publisher: Hindawi Limited
Date: 2011
DOI: 10.1155/2011/194720
Abstract: Cell therapy has been established as an important field of research with considerable progress in the last years. At the same time, the progressive aging of the population has highlighted the importance of discovering therapeutic alternatives for diseases of high incidence and disability, such as stroke. Menstrual blood is a recently discovered source of stem cells with potential relevance for the treatment of stroke. Migration to the infarct site, modulation of the inflammatory reaction, secretion of neurotrophic factors, and possible differentiation warrant these cells as therapeutic tools. We here propose the use of autologous menstrual blood cells in the restorative treatment of the subacute phase of stroke. We highlight the availability, proliferative capacity, pluripotency, and angiogenic features of these cells and explore their mechanistic pathways of repair. Practical aspects of clinical application of menstrual blood cells for stroke will be discussed, from cell harvesting and cryopreservation to administration to the patient.
Publisher: Society for Neuroscience
Date: 09-2021
DOI: 10.1523/ENEURO.0314-21.2021
Abstract: Convincing evidence of blood-spinal cord barrier (BSCB) alterations has been demonstrated in amyotrophic lateral sclerosis (ALS) and barrier repair is imperative to prevent motor neuron dysfunction. We showed benefits of human bone marrow-derived CD34+ cells (hBM34+) and endothelial progenitor cells (hBM-EPCs) intravenous transplantation into symptomatic G93A SOD1 mutant mice on barrier reparative processes. These gains likely occurred by replacement of damaged endothelial cells, prolonging motor neuron survival. However, additional investigations are needed to confirm the effects of administered cells on integrity of the microvascular endothelium. The aim of this study was to determine tight junction protein levels, capillary pericyte coverage, microvascular basement membrane, and endothelial filamentous actin (F-actin) status in spinal cord capillaries of G93A SOD1 mutant mice treated with human bone marrow-derived stem cells. Tight junction proteins were detected in the spinal cords of cell-treated versus non-treated mice via Western blotting at four weeks after transplant. Capillary pericyte, basement membrane laminin, and endothelial F-actin magnitudes were determined in cervical/lumbar spinal cord tissues in ALS mice, including controls, by immunohistochemistry and fluorescent staining. Results showed that cell-treated versus media-treated ALS mice substantially increased tight junction protein levels, capillary pericyte coverage, basement membrane laminin immunoexpressions, and endothelial cytoskeletal F-actin fluorescent expressions. The greatest benefits were detected in mice receiving hBM-EPCs versus hBM34+ cells. These study results support treatment with a specific cell type derived from human bone marrow toward BSCB repair in ALS. Thus, hBM-EPCs may be advanced for clinical applications as a cell-specific approach for ALS therapy through restored barrier integrity.
Publisher: Springer Science and Business Media LLC
Date: 19-06-2015
DOI: 10.1038/SREP11322
Abstract: BACE1 initiates amyloid-β (Aβ) generation and the resultant cerebral amyloidosis, as a characteristic of Alzheimer’s disease (AD). Thus, inhibition of BACE1 has been the focus of a large body of research. The most recent clinical trials highlight the difficulty involved in this type of anti-AD therapy as evidenced by side effects likely due to the ubiquitous nature of BACE1, which cleaves multiple substrates. The human Swedish mutant form of amyloid protein precursor (APPswe) has been shown to possess a higher affinity for BACE1 compared to wild-type APP (APPwt). We pursued a new approach wherein harnessing this greater affinity to modulate BACE1 APP processing activity. We found that one peptide derived from APPswe, containing the β-cleavage site, strongly inhibits BACE1 activity and thereby reduces Aβ production. This peptide, termed APPswe BACE1 binding site peptide (APPsweBBP), was further conjugated to the fusion domain of the HIV-1 Tat protein (TAT) at the C-terminus to facilitate its biomembrane-penetrating activity. APPwt and APPswe over-expressing CHO cells treated with this TAT-conjugated peptide resulted in a marked reduction of Aβ and a significant increase of soluble APPα. Intraperitoneal administration of this peptide to 5XFAD mice markedly reduced β-amyloid deposits as well as improved hippoc al-dependent learning and memory.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Informa UK Limited
Date: 08-05-2017
DOI: 10.1080/14712598.2017.1323862
Abstract: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord. Treatment options are limited due to the complexity of underlying disease factors. Cell therapy, using human umbilical cord blood (hUCB) cells may be a promising new treatment for ALS, mainly by providing a protective microenvironment for motor neuron survival. Areas covered: Composition, in vitro and in vivo differentiation of hUCB cells, and the advantages of cord blood as a source of transplant cells are discussed. A brief history of hUCB in treatment of an ALS animal model and the feasibility of these cells in therapy for ALS patients is provided. Current ALS clinical trials are also deliberated. Expert opinion: Among multiple advantages, hUCB cells' production of various anti-inflammatory/growth/trophic factors makes them an attractive cell source for ALS therapy. Biodistribution and optimal hUCB cell dose for transplantation have been determined in preclinical studies. Repeated intravenous cell doses during disease progression may be the best approach for cell-based ALS treatment. Accumulated evidence shows the efficacy of naïve or genetically modified MNC hUCB cells in the treatment of ALS and provide a superior basis for the development of clinical trials in the near future.
Publisher: Medknow
Date: 2015
Publisher: Bentham Science Publishers Ltd.
Date: 07-2008
DOI: 10.2174/1874609810801020105
Abstract: The impact of intraventricular ciliary neurotrophic factor (CNTF) on motor function in aged rats was evaluated. Spontaneous locomotion and motor coordination were quantified in young (5-6 months) and aged (24-25 months) rats. Relative to young animals, aged rats were significantly less active, fell more rapidly from a rotating rod, and were unable to maintain their balance on a wooden beam. Aged animals received bilateral intraventricular implants of polymer-encapsulated fibroblasts that were genetically modified to secrete CNTF. Controls received either no implant or capsules loaded with mock transfected cells. One month after implantation the aged animals that received CNTF implants were significantly more active and were improved on the rotorod and beam balance tests. The improvement in performance on the rotorod and beam balance tests was dependant on the task difficulty and dissipated at higher rotations (rotorod) and smaller beam widths (beam balance). No recovery was seen in aged animals receiving control implants. Postmortem removal of the encapsulated cells confirmed that they continued to secrete CNTF. These data are the first to suggest that intracerebral delivery of CNTF might be useful for slowing or reversing age-related changes in motor function.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Springer Netherlands
Date: 06-09-2011
Publisher: Wiley
Date: 09-2009
Publisher: Oxford University Press (OUP)
Date: 20-04-2019
Abstract: The United States has been actively involved in major armed conflicts over the last 15 years. As a result, a significant proportion of active duty service personnel and returning veterans have endured combat, putting them at risk for developing post-traumatic stress disorder (PTSD), a disabling disorder that may occur after exposure to a traumatic event. Current therapies often require long-term, time-intensive and costly commitment from the patient and have variable degrees of success. There remains an ongoing need for better therapies, including complementary medicine approaches that can effectively reduce PTSD symptoms. While anecdotal evidence suggests that routine practice of Brazilian Jiu Jitsu (BJJ) can reduce symptoms of PTSD, there have been no formal studies to address this. This study was approved by the University of South Florida Institutional Review Board (#PRO00019430). Male US active duty service members and veterans from the T a area participated in a 5-month (40 sessions) BJJ training program. Before beginning and again midway through and upon completion of training the participants completed several validated self-report measures that addressed symptoms of PTSD and other co-morbid conditions. Effect size and 95% confidence intervals were determined using a within-person single-group pretest–posttest design. Study participants demonstrated clinically meaningful improvements in their PTSD symptoms as well as decreased symptoms of major depressive disorder, generalized anxiety and decreased alcohol use effect sizes varied from 0.80 to 1.85. The results from this first-of-kind pilot study suggest that including BJJ as a complementary treatment to standard therapy for PTSD may be of value. It will be necessary to validate these promising results with a larger subject cohort and a more rigorous experimental design before routinely recommending this complementary therapy.
Publisher: Bentham Science Publishers Ltd.
Date: 17-03-2011
Publisher: SAGE Publications
Date: 02-2007
DOI: 10.3727/000000007783464623
Abstract: Umbilical cord blood (UCB) banking has become a new obstetrical trend. It offers expectant parents a biological insurance policy that can be used in the event of a child or family member's life-threatening illness and puts patients in a position of control over their own treatment options. However, its graduation to conventional therapy in the clinical realm relies on breakthrough research that will prove its efficacy for a range of ailments. Expanding the multipotent cells found within the mononuclear fraction of UCB so that adequate dosing can be achieved, effectively expanding desired cells ex vivo, establishing its safety and limitations in HLA-mismatched recipients, defining its mechanisms of action, and proving its utility in a wide variety of both rare and common illnesses and diseases are a few of the challenges left to tackle. Nevertheless, the field is moving fast and new UCB-based therapies are on the horizon.
Publisher: Public Library of Science (PLoS)
Date: 12-05-2010
Publisher: Elsevier
Date: 2012
Publisher: Future Medicine Ltd
Date: 2010
DOI: 10.2217/RME.09.71
Abstract: Aims: We investigated whether human umbilical cord blood mononuclear cells (HUCBC) can limit progressive cardiomyopathy in TO2 hamsters. Materials & methods: A total of 22 TO2 1-month-old hamsters were treated with intramyocardial HUCBC, 4 × 10 6 in Isolyte ® , and 23 TO2 1-month-old hamsters were treated with intramyocardial Isolyte. A total of 16 1-month-old F1B hamsters served as controls and received intramyocardial Isolyte. Echocardiograms were performed on all hamsters prior to and monthly after treatment for 6 months. Heart tissues were then stained with hematoxylin and eosin, Masson’s Trichrome and human leukocyte antibody. Results: In F1B hamsters, left ventricular fractional shortening (FS) and ejection fractions (EF) did not significantly decrease over 6 months. By contrast, in Isolyte-treated TO2 hamsters, FS decreased from 56.2 ± 1.0% to 19.7 ± 3.2% and EF decreased from 89.5 ± 1.4% to 44.9 ± 5.9% at 6 months (both p 0.0001). The FS and EF in HUCBC-treated TO2 hamsters also progressively decreased over 6 months but the changes were more gradual, especially during the first month after HUCBC treatment when FS was 52.0 ± 1.5% and EF was 89.5 ± 1.4%, which was not significantly different from the FS and EF in the F1B hamsters. Moreover, in the HUCBC-treated hamsters, the FS and EF were 20–30% greater than FS and EF in Isolyte TO2 hamsters at 3 and 5 months (p 0.01). In Isolyte-treated TO2 hamsters at 6–7 months, fibrosis involved 30.0 ± 5.0% of left ventricle and 35.0 ± 5.0% of septum. By contrast, in HUCBC-treated hamsters, fibrosis involved only 6.5 ± 2.3% of the left ventricle and 6.3 ± 1.8% of septum (p 0.05). The average number of blood vessels per myocardial microscopic field in HUCBC-treated hearts was 53.5 ± 0.8 versus 46.2 ± 3.0 in Isolyte-treated TO2 hearts (p 0.05). Conclusion: HUCBC, when given as a single intramyocardial injection, can limit fibrosis and increase heart function over the short term in TO2 hamsters with cardiomyopathy.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.NEUROPHARM.2016.03.035
Abstract: Amyotrophic lateral sclerosis (ALS) is a lethal degenerating disease, characterized by progressive muscular atrophy without any effective treatment. Here, we demonstrated the efficacy of abrograting autophagy in motor neurons (MN) by treatment with n-butylidenephthalide (n-BP) in ALS transgenic mice (SOD1(G93A)). Pre-symptomatic oral administration of 250 mg/kg/bid n-BP significantly prolonged the survival period (203.9 ± 18.3 days), improved motor function, and attenuated MN loss compared to vehicle control (126.4 ± 7.2 days). This prolonged survival of ALS mice is much more robust than that reported with riluzole (140 days), which is an approved clinical therapy for ALS. The therapeutic mechanism targeted by n-BP involved the autophagic pathway as evidenced by decreased LC3-II expression (a biomarker of autophagy), enhanced mTOR levels, and attenuated autophagic activity, altogether increasing MN survival in a dose-dependent manner. This result was also confirmed by double transgenic mice (SOD1(G93A):LC3-GFP) which showed that oral administration of n-BP reduced GFP density and decreased caspase-3 expression. In addition, electron microscopy revealed that n-BP administration not only decreased autophagosome number but also reduced morphological dysfunction of mitochondria. In summary, these results indicate that down-regulation of autophagy activation via n-BP may pose as a therapeutic regimen for ALS and relevant neurodegenerative diseases.
Publisher: Springer International Publishing
Date: 2018
DOI: 10.1007/978-3-319-93485-3_2
Abstract: Human somatic stem cells can be identified and isolated from different types of tissues and are grouped here based on their developmental maturation and ability to undergo neural differentiation. The first group will represent afterbirth somatic tissues, which are perinatal stem cells including placental blood and tissue, amniotic fluid and tissue, and umbilical cord blood- and umbilical cord tissue-derived cells. The second group of cells discussed in this chapter is the adult stem cells, generally those in a transient period of development, thus placing them in the special position of transitioning from the perinatal to young somatic tissue, and they include the menstrual blood-, the peripheral blood-, and the bone marrow-derived stem cells.
Publisher: SAGE Publications
Date: 09-2011
Abstract: The following commentary provides a discussion of the articles published in Technology and Innovation in 2010 and where possible places them into context with those reported in Cell Transplantation. These articles can be ided into the following topics: a) models for innovation and technological commercialization, b) the ethical and legal consequences of the emergence of new technologies, c) research on novel technologies and methods, and d) the difficulties involved in peer review and scientific assessment. The articles shed light on the effects of technological innovation and commercialization on scientific ethical regulation, the establishment of legal standards for the protection of intellectual property, and the development of financial models.
Publisher: SAGE Publications
Date: 05-2017
Publisher: Springer Science and Business Media LLC
Date: 25-09-2008
Abstract: It is well known that most neurodegenerative diseases are associated with microglia-mediated inflammation. Our previous research demonstrates that the CD40 signaling is critically involved in microglia-related immune responses in the brain. For ex le, it is well known that the activation of the signal transducer and activator of transcription (STAT) signaling pathway plays a central role in interferon-gamma (IFN-γ)-induced microglial CD40 expression. We and others have previously reported that microglial CD40 expression is significantly induced by IFN-γ and amyloid-β (Aβ) peptide. Recent studies have shown that certain flavonoids possess anti-inflammatory and neuroprotective properties distinct from their well-known anti-oxidant effects. In particular, flavonoids, apigenin and luteolin have been found to be effective CD40 immunomodulators. Cultured microglia, both N9 and primary derived lines, were treated with flavonoids in the presence of IFN-γ and/or CD40 ligation to assess any anti-inflammatory effects and/or mechanisms. CD40 expression on microglia was analyzed by fluorescence activated cell sorting (FACS). Anti-inflammatory effects and mechanisms were confirmed by ELISA for interlekin-6 (IL-6) and TNF-α, lactate dehydrogenase (LDH) assay, and STAT1 Western blotting. Apigenin and luteolin concentration-dependently suppressed IFN-γ-induced CD40 expression. Apigenin and luteolin also suppressed microglial TNF-α and IL-6 production stimulated by IFN-gamma challenge in the presence of CD40 ligation. In addition, apigenin and luteolin markedly inhibited IFN-γ-induced phosphorylation of STAT1 with little impact on cell survival. Our findings provide further support for apigenin and luteolin's anti-inflammatory effects and suggest that these flavonoids may have neuroprotective/disease-modifying properties in various neurodegenerative disorders, including Alzheimer's disease (AD).
Publisher: IOP Publishing
Date: 04-04-2007
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.JNEUMETH.2009.02.016
Abstract: Cerebral blood flow is impaired during middle cerebral artery occlusion in the rat model of stroke. However, the long term effects on cerebral blood flow following occlusion have received little attention. We examined cerebral blood flow in both sides at multiple time points following middle cerebral artery occlusion of the rat. The bilateral cerebral blood flow in young male Sprague Dawley rats was measured at the time of occlusion, as well as 4, 10 and 16 weeks after occlusion. Under the present experimental conditions, the difference between the left and right side's cerebral blood flow was observed to appear to switch in direction in a visual oscillatory fashion over time in the sham-treated group, whereas the occluded animals consistently showed left side dominance. One group of rats was intraparenchymally transplanted with a human neural stem cell line (CTX0E03 cells) known to have benefit in stroke models. Cerebral blood flow in the lesioned side of the cell-treated group was observed to be improved compared to the untreated rats and to demonstrate a similar oscillatory nature as that observed in sham-treated animals. These findings suggest that multiple bilateral monitoring of cerebral blood flow over time can show effects of stem cell transplantation efficiently as well as functional tests in an animal stroke model.
Publisher: Public Library of Science (PLoS)
Date: 03-02-2012
Publisher: Mary Ann Liebert Inc
Date: 02-2014
Publisher: Springer Science and Business Media LLC
Date: 14-08-2014
Abstract: Alzheimer’s disease (AD), a progressive neurodegenerative disorder that is the most common cause of dementia in the elderly, is characterized by the accumulation of amyloid- β (A β ) plaques and neurofibrillary tangles, as well as a progressive loss of synapses and neurons in the brain. The major pertinacious component of amyloid plaques is A β , a variably sized peptide derived from the integral membrane protein amyloid precursor protein (APP). The A β region of APP locates partly within its ecto- and trans-membrane domains. APP is cleaved by three proteases, designated as α -, β -, and γ -secretases. Processing by β - and γ -secretase cleaves the N- and C-terminal ends of the A β region, respectively, releasing A β , whereas α -secretase cleaves within the A β sequence, releasing soluble APP α (sAPP α ). The γ -secretase cleaves at several adjacent sites to yield A β species containing 39–43 amino acid residues. Both α - and β -cleavage sites of human wild-type APP are located in APP 672–699 region (ectodomain of β -C-terminal fragment, ED- β -CTF or ED-C99). Therefore, the amino acid residues within or near this region are definitely pivotal for human wild-type APP function and processing. Here, we report that one ED-C99-specific monoclonal antibody (mAb ED-C99 ) blocks human wild-type APP endocytosis and shifts its processing from α - to β -cleavage, as evidenced by elevated accumulation of cell surface full-length APP and β -CTF together with reduced sAPP α and α -CTF levels. Moreover, mAb ED-C99 enhances the interactions of APP with cholesterol. Consistently, intracerebroventricular injection of mAb ED-C99 to human wild-type APP transgenic mice markedly increases membrane-associated β -CTF. All these findings suggest that APP 672–699 region is critical for human wild-type APP processing and may provide new clues for the pathogenesis of sporadic AD.
Publisher: Springer Science and Business Media LLC
Date: 03-05-2012
DOI: 10.1007/S12975-012-0177-6
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron death, leading to muscle atrophy, paralysis, and death usually within 3 to 5 years after diagnosis. Most cases are sporadic, with still undefined etiopathogenesis. Both the innate and adaptive immune systems are involved in ALS, with special participation of T lymphocytes and microglia. Inflammation plays a dual role in the disease, protective and T regulatory cell rich in the early stages and deleterious as disease progresses. Attempts to modulate immune/inflammatory system response are reported in the literature, and while beneficial effects are achieved in ALS animal models, results of most clinical trials have been disappointing. The impaired blood-brain barrier is an important feature in the pathogenesis of ALS and likely affects the immune system response. The present review describes the role of the immune system in ALS pathogenesis and the tight coupling of immunity and central nervous system barrier function.
Publisher: Springer Science and Business Media LLC
Date: 09-2007
DOI: 10.1007/BF03033564
Publisher: SAGE Publications
Date: 04-2018
Abstract: Alzheimer’s Disease (AD) is the leading cause of dementia in the elderly. In healthy in iduals, amyloid precursor protein (APP) is cleaved by α-secretase, generating soluble α-amyloid precursor protein (sAPPα), which contributes neuroprotective functions in the neuronal environment. In contrast, in the neurodegenerative environment of AD patients, amyloid-β-peptide (Aβ) of either 40 or 42 residues are generated by increased activity of β- and γ-secretase. These proteins amalgamate in specific regions of the brain, which disrupts neuronal functions and leads to cognitive impairment. Human umbilical cord blood cells (HUCBC) have proven useful as potential immunomodulatory therapies in various models of neurodegenerative diseases, including AD. Our most recent work studied the impact of umbilical cord blood serum (CBS) on modulation of sAPPα production. Heat-sensitive CBS significantly promoted sAPPα production, indicating that heat-sensitive factor(s) play(s) a role in this process. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis was used to determine the molecular source of α-secretase in purified CBS and aged blood serum (AgBS) fraction. Of the proteins identified, the subunits of C1 complex (C1q, C1r, and C1s) and alpha-2-macroglobulin showed significantly greater levels in purified α-CBS fraction (α-CBSF) compared with the AgBS fraction (AgBSF). Specifically, C1 markedly increased sAPPα and alpha-carboxyl-terminal fragment (α-CTF) production in a dose-dependent fashion, whereas C1q alone only minimally increased and C3 did not increase sAPPα production in the absence of sera. Furthermore, C1q markedly increased sAPPα and α-CTF, while decreasing Aβ, in CHO/APPwt cells cultured in the presence of whole sera. These results confirm our initial assumption that APP α-secretase activity in human blood serum is mediated by complement C1, opening a potential therapeutic modality for the future of AD.
Publisher: Wiley
Date: 04-2010
Publisher: Wiley
Date: 09-07-2014
DOI: 10.1002/CNE.23582
Publisher: SAGE Publications
Date: 04-2015
Abstract: Human umbilical cord blood (HUCB) cell therapies have shown promising results in reducing brain infarct volume and most importantly in improving neurobehavioral function in rat permanent middle cerebral artery occlusion, a model of stroke. In this study, we examined the gene expression profile in neurons subjected to oxygen-glucose deprivation (OGD) with or without HUCB treatment and identified signaling pathways (Akt/MAPK) important in eliciting HUCB-mediated neuroprotective responses. Gene chip microarray analysis was performed using RNA s les extracted from the neuronal cell cultures from four experimental groups: normoxia, normoxia + HUCB, OGD, and OGD + HUCB. Both quantitative RT-PCR and immunohistochemistry were carried out to verify the microarray results. Using the Genomatix software program, promoter regions of selected genes were compared to reveal common transcription factor-binding sites and, subsequently, signal transduction pathways. Under OGD condition, HUCB cells significantly reduced neuronal loss from 68% to 44% [one-way ANOVA, F(3, 16) = 11, p = 0.0003]. Microarray analysis identified mRNA expression of Prdx5, Vcam1, CCL20, Alcam, and Pax6 as being significantly altered by HUCB cell treatment. Inhibition of the Akt pathway significantly abolished the neuroprotective effect of HUCB cells [one-way ANOVA, F(3, 11) = 8.663, p = 0.0031]. Our observations show that HUCB neuroprotection is dependent on the activation of the Akt signaling pathway that increases transcription of the Prdx5 gene. We concluded that HUCB cell therapy would be a promising treatment for stroke and other forms of brain injury by modifying acute gene expression to promote neural cell protection.
Publisher: SAGE Publications
Date: 06-2015
Abstract: Mononuclear stem cells have been studied for their potential in myocardial ischemia. In our previous published article, ReACT ® phase I/II clinical trial, our results suggest that a certain cell population, promonocytes, directly correlated with the perceived angiogenesis in refractory angina patients. This study is ReACT's clinical update, assessing long-term sustained efficacy. The ReACT phase IIA/B noncontrolled, open-label, clinical trial enrolled 14 patients with refractory angina and viable ischemic myocardium, without ventricular dysfunction, who were not suitable for myocardial revascularization. The procedure consisted of direct myocardial injection of a specific mononuclear cell formulation, with a certain percentage of promonocytes, in a single series of multiple injections (24—90 0.2 ml each) into specific areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at the 12-month follow-up and ischemic area reduction (scintigraphic analysis) at the 12-month follow-up, in correlation with ReACT's formulation. A recovery index (for patients with more than 1 year follow-up) was created to evaluate CCSAC over time, until April 2011. Almost all patients presented progressive improvement in CCSAC beginning 3 months ( p = 0.002) postprocedure, which was sustained at the 12-month follow-up ( p = 0.002), as well as objective myocardium ischemic area reduction at 6 months (decrease of 15%, p 0.024) and 12 months (decrease of 100%, p 0.004) The recovery index ( n = 10) showed that the patients were graded less than CCSAC 4 for 73.9 ± 24.2% over a median follow-up time of 46.8 months. After characterization, ReACT's promonocyte concentration suggested a positive correlation with CCSAC improvement ( r = −0.575, p = 0.082). Quality of life (SF-36 questionnaire) improved significantly in almost all domains. Cost-effectiveness analysis showed decrease in angina-related direct costs. Refractory angina patients presented a sustained long-term improvement in CCSAC and myocardium ischemic areas after the procedure. The long-term follow-up and strong improvement in quality of life reinforce effectiveness. Promonocytes may play a key role in myocardial neoangiogenesis. ReACT dramatically decreased direct costs.
Publisher: Springer Science and Business Media LLC
Date: 10-2013
DOI: 10.1038/502448B
Publisher: Springer New York
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 07-08-2010
DOI: 10.1007/S12015-010-9181-Y
Abstract: As scientists position themselves in translating the therapeutic potential of stem cells from laboratory to clinical applications, publishing companies have taken this rapidly evolving field as a unique opportunity to launch new journals for dissemination of stem cell research. Over the last decade, the significant increase in the number of stem cell-based journals has created a conundrum. At stake is the pressure for these new journals to build their reputation by maintaining publication standards, while at the same time attracting a cadre of stem cell researchers to consider their journals as the publication of choice. We discuss here a prophetic path of survival for these journals which likely will closely mimic the core scientific and translational value of stem cells, namely their capacity to proliferate and differentiate into something meaningful!
Publisher: Elsevier BV
Date: 05-2021
Publisher: Springer London
Date: 30-09-2014
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.TRSL.2012.02.004
Abstract: We have previously reported that human umbilical cord blood mononuclear cells (HUCBC), which contain hematopoietic, mesenchymal, and endothelial stem cells, can significantly reduce acute myocardial infarction size. To determine the mechanism whereby HUCBC increase myocyte and vascular endothelial cell survival, we treated cardiac myocytes and coronary artery endothelial cells in separate experiments with HUCBC plus culture media or culture media alone and subjected the cells to 24 h of hypoxia or normoxia. We then determined in myocytes and endothelial cells activation of the cell survival protein Akt by Western blots. We also determined in these cells apoptosis by annexin V staining and necrosis by propidium iodide staining. Thereafter, we inhibited with API, a specific and sensitive Akt inhibitor, Akt activation in myocytes and endothelial cells cultured with HUCBC during hypoxia and determined cell apoptosis and necrosis. In cells cultured without HUCBC, hypoxia only slightly activated Akt. Moreover, hypoxia increased myocyte apoptosis by ≥ 226% and necrosis by 58% in comparison with myocytes in normoxia. Hypoxic treatment of endothelial cells without HUCBC increased apoptosis by 94% and necrosis by 59%. In contrast, hypoxia did not significantly affect HUCBC. Moreover, in myocyte + HUCBC cultures in hypoxia, HUCBC induced a ≥ 135% increase in myocyte phospho-Akt. Akt activation decreased myocyte apoptosis by 76% and necrosis by 35%. In endothelial cells, HUCBC increased phospho-Akt by 116%. HUCBC also decreased endothelial cell apoptosis by 58% and necrosis by 42%. Inhibition of Akt with API in myocytes and endothelial cells cultured with HUCBC during hypoxia nearly totally prevented the HUCBC-induced decrease in apoptosis and necrosis. We conclude that HUCBC can significantly decrease hypoxia-induced myocyte and endothelial cell apoptosis and necrosis by activating Akt in these cells and in this manner HUCBC can limit myocardial ischemia and injury.
Publisher: SAGE Publications
Date: 04-2016
Publisher: SAGE Publications
Date: 08-2016
Abstract: Blood–brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague–Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.
Publisher: Bentham Science Publishers Ltd.
Date: 08-2012
Publisher: Springer Vienna
Date: 27-11-2012
Publisher: Proceedings of the National Academy of Sciences
Date: 28-04-2014
Abstract: There is national and international recognition of the importance of innovation, technology transfer, and entrepreneurship for sustained economic revival. With the decline of industrial research laboratories in the United States, research universities are being asked to play a central role in our knowledge-centered economy by the technology transfer of their discoveries, innovations, and inventions. In response to this challenge, innovation ecologies at and around universities are starting to change. However, the change has been slow and limited. The authors believe this can be attributed partially to a lack of change in incentives for the central stakeholder, the faculty member. The authors have taken the position that universities should expand their criteria to treat patents, licensing, and commercialization activity by faculty as an important consideration for merit, tenure, and career advancement, along with publishing, teaching, and service. This position is placed in a historical context with a look at the history of tenure in the United States, patents, and licensing at universities, the current status of university tenure and career advancement processes, and models for the future.
Publisher: SAGE Publications
Date: 10-2007
DOI: 10.3727/096368907783338299
Abstract: There is no consensus regarding the optimal dose of stem cells or the optimal route of administration for the treatment of acute myocardial infarction. Bone marrow cells, containing hematopoietic and mesenchymal stem cells, in doses of 0.5 × 106 to × 106 have been directly injected into the myocardium or into coronary arteries or infused intravenously in subjects with myocardial infarctions to reduce infarct size and improve heart function. Therefore, we determined the specific effects of different doses of human umbilical cord blood mononuclear cells (HUCBC), which contain hematopoietic and mesenchymal stem cells, on infarct size. In order to determine the optimal technique for stem cell administration, HUCBC were injected directly into the myocardium (IM), or into the LV cavity with the ascending aorta transiently cl ed to facilitate coronary artery perfusion (IA), or injected intravenously (IV) in rats 1–2 h after the left anterior coronary artery was permanently ligated. Immune suppressive therapy was not given to any rat. One month later, the infarct size in control rat hearts treated with only Isolyte averaged 23.7 ± 1.7% of the LV muscle area. Intramyocardial injection of HUCBC reduced the infarct size by 71% with 0.5 × 106 HUCBC and by 93% with 4 × 106 HUCBC in comparison with the controls (p 0. 001). Intracoronary injection reduced the infarction size by 47% with 0.5 × 106 HUCBC and by 80% with 4 × 106 HUCBC (p 0. 001), and IV HUCBC reduced infarct size by 51% with 0.5 × 106 and by 75–77% with 16–32 million HUCBC (p 0. 001) in comparison with control hearts. With 4 × 106 HUCBC, infarction size was 65% smaller with IM HUCBC than with IA HUCBC and 78% smaller than with IV HUCBC (p 0. 05). Nevertheless, IM, IA, and IV HUCBC all produced significant reductions in infarct size in comparison with Isolyte-treated infarcted hearts without requirements for host immune suppression. The present experiments demonstrate that the optimal dose of HUCBC for reduction of infarct size in the rat is 4 × 106 IM, 4 × 106 IA, and 16 × 106 IV, and that the IM injection of HUCBC is the most effective technique for reduction in infarct size.
Publisher: MDPI AG
Date: 28-08-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2019
DOI: 10.1161/STROKEAHA.119.025249
Abstract: Retinal ischemia is a major cause of visual impairment in stroke patients, but our incomplete understanding of its pathology may contribute to a lack of effective treatment. Here, we investigated the role of mitochondrial dysfunction in retinal ischemia and probed the potential of mesenchymal stem cells (MSCs) in mitochondrial repair under such pathological condition. In vivo, rats were subjected to middle cerebral artery occlusion then randomly treated with intravenous MSCs or vehicle. Laser Doppler was used to evaluate the blood flow in the brain and the eye, while immunohistochemical staining assessed cellular degeneration at days 3 and 14 poststroke. In vitro, retinal pigmented epithelium cells were exposed to either oxygen-glucose deprivation or oxygen-glucose deprivation and coculture with MSCs, and subsequently, cell death and mitochondrial function were examined immunocytochemically and with Seahorse analyzer, respectively. Middle cerebral artery occlusion significantly reduced blood flow in the brain and the eye accompanied by mitochondrial dysfunction and ganglion cell death at days 3 and 14 poststroke. Intravenous MSCs elicited mitochondrial repair and improved ganglion cell survival at day 14 poststroke. Oxygen-glucose deprivation similarly induced mitochondrial dysfunction and cell death in retinal pigmented epithelium cells coculture with MSCs restored mitochondrial respiration, mitochondrial network morphology, and mitochondrial dynamics, which likely attenuated oxygen-glucose deprivation-mediated retinal pigmented epithelium cell death. Retinal ischemia is closely associated with mitochondrial dysfunction, which can be remedied by stem cell-mediated mitochondrial repair.
Publisher: Oxford University Press (OUP)
Date: 09-06-2016
DOI: 10.1093/JNEN/NLW040
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.PNPBP.2014.05.016
Abstract: Fetal alcohol spectrum disorder (FASD) is caused by intrauterine exposure to alcohol and can cause a full range of abnormalities to brain development, as well as long-term sequelae of cognitive, sensory and motor impairments. The incidence is estimated to be as high as 2% to 5% in children born within the US, however the prevalence is even higher in low socioeconomic populations. Despite the various mechanisms thought to explain the etiology of FASD, molecular targets of ethanol toxicity during development are not completely understood. More recent findings explore the role of GABA-A and GABA-B mechanisms, as well as cell death, cell signaling and gene expression malfunctions. Stem cell based therapies have grown exponentially over the last decade, which have lead to novel clinical interventions across many disciplines. Thus, early detailed understanding of the therapeutic potential of stem cell research has provided promising applications across a wide range of illnesses. Consequently, these potential benefits may ultimately lead to a reduced incidence and severity of this highly preventable and prevalent birth defect. It is recognized that stem cell derivations provide unique difficulties and limitations of therapeutic applications. This review will outline the current knowledge, along with the benefits and challenges of stem cell therapy for FASD.
Publisher: Elsevier
Date: 2012
Publisher: SAGE Publications
Date: 07-2009
Publisher: Mary Ann Liebert Inc
Date: 10-2008
Publisher: Bentham Science Publishers Ltd.
Date: 02-07-2015
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-05-2018
Publisher: American Association for the Advancement of Science (AAAS)
Date: 21-11-2014
Publisher: University of Western Ontario, Western Libraries
Date: 07-04-2014
Abstract: This article presents a case study of an exercise in Aboriginal community governance in Australia. It sets out the background events that led the Yawuru Native Title Holders Aboriginal Corporation in the town of Broome on Australia’s northwest coast to secure information for its own needs as an act of self-determination and essential governance, and it presents some of the key findings from that exercise. As the Indigenous rights agenda shifts from the pursuit of restitution to the management and implementation of benefits, those with proprietary rights are finding it increasingly necessary to build internal capacity for post-native title governance and community planning, including in the area of information retrieval and application. As an incorporated land-holding group, the Yawuru people of Broome are amongst the first in Australia to move in this area of information gathering, certainly in terms of the degree of local control, participation, and conceptual thinking around the logistics and rationale for such an exercise. An innovative addition has been the incorporation of survey output data into a Geographic Information System to provide for spatial analysis and a decision support mechanism for local community planning. In launching and administering the "Knowing our Community" household survey in Broome, the Yawuru have set a precedent in the acquisition and application of demographic information for internal planning and community development in the post-native title determination era.
Publisher: Public Library of Science (PLoS)
Date: 24-10-2013
Publisher: Springer Science and Business Media LLC
Date: 13-08-2020
DOI: 10.1007/S12015-020-10026-5
Abstract: The human population is in the midst of battling a rapidly-spreading virus— Severe Acute Respiratory Syndrome Coronavirus 2, responsible for Coronavirus disease 2019 or COVID-19. Despite the resurgences in positive cases after reopening businesses in May, the country is seeing a shift in mindset surrounding the pandemic as people have been eagerly trickling out from federally-mandated quarantine into restaurants, bars, and gyms across America. History can teach us about the past, and today’s pandemic is no exception. Without a vaccine available, three lessons from the 1918 Spanish flu pandemic may arm us in our fight against COVID-19. First, those who survived the first wave developed immunity to the second wave, highlighting the potential of passive immunity-based treatments like convalescent plasma and cell-based therapy. Second, the long-term consequences of COVID-19 are unknown. Slow-progressive cases of the Spanish flu have been linked to bacterial pneumonia and neurological disorders later in life, emphasizing the need to reduce COVID-19 transmission. Third, the Spanish flu killed approximately 17 to 50 million people, and the lack of human response, overcrowding, and poor hygiene were key in promoting the spread and high mortality. Human behavior is the most important strategy for preventing the virus spread and we must adhere to proper precautions. This review will cover our current understanding of the pathology and treatment for COVID-19 and highlight similarities between past pandemics. By revisiting history, we hope to emphasize the importance of human behavior and innovative therapies as we wait for the development of a vaccine.
Publisher: SAGE Publications
Date: 11-2015
Abstract: Alzheimer's disease (AD) is the fourth major cause of mortality in the elderly in the US and the leading cause of dementia worldwide. While pharmacological targets have been discovered, there are no true disease-modifying therapies. We have recently discovered that multiple low-dose infusions of human umbilical cord blood cells (HUCBCs) ameliorate cognitive impairments and reduce Aβ-associated neuropathology in PSAPP transgenic mice. However, the mechanism for these effects of HUCBCs remains unclear. In the present study, we examined whether monocytes, as important components of HUCBCs, would have beneficial outcomes on the reduction of AD-like pathology and associated cognitive impairments in PSAPP transgenic AD model mice. PSAPP mice and their wild-type littermates were treated monthly with an infusion of peripheral human umbilical cord blood cell (HUCBC)-derived monocytes over a period of 2 and 4 months, followed by behavioral evaluations, biochemical, and histological analyses. The principal findings of the present study confirmed that monocytes derived from HUCBCs (CB-M) play a central role in HUCBC-mediated cognition-enhancing and Aβ pathology-ameliorating activities. Most importantly, we found that compared with CB-M, aged monocytes showed an ineffective phagocytosis of Aβ, while exogenous soluble amyloid precursor protein α (sAPPα) could reverse this deficiency. Pretreating monocytes with sAPPα upregulates Aβ internalization. Our further studies suggested that sAPPα could form a heterodimer with Aβs, with the APP 672-688 (Aβ 1-16 ) region being responsible for this effect. This in turn promoted binding of these heterodimers to monocyte scavenger receptors and thus promoted enhanced Aβ clearance. In summary, our findings suggest an interesting hypothesis that peripheral monocytes contribute to Aβ clearance through heterodimerization of sAPPα with Aβ. Further, declined or impaired sAPPaα production, or reduced heterodimerization with Aβ, would cause a deficiency in Aβ clearance and thus accelerate the pathogenesis of AD.
Publisher: SAGE Publications
Date: 12-2018
Abstract: As guest editors of this special issue, we are delighted to present 13 articles that discuss advances in stroke research including translational stroke research, stroke research milestones, and proposals for future directions. Stroke is a major cause of disability, and, according to the Centers for Disease Control and Prevention, is the fifth leading cause of death in the US alone. Possible factors contributing to stroke pathogenesis are elucidated and possible treatment modalities are explored in the following special issue of Cell Transplantation.
Publisher: SAGE Publications
Date: 08-2007
Publisher: Bentham Science Publishers Ltd.
Date: 15-01-2020
DOI: 10.2174/1871527318666191021145252
Abstract: Here, we summarized recent advances in laboratory and clinical research on gut microbiome. The goal is to highlight recent discoveries on the biology and behavioral manifestations of gut microbiomes under normal and pathologic conditions. With this new scientific knowledge, we wish to cultivate cross-fertilization of science across multi-disciplines in the hopes of exploiting the gut microbiome as a key component of human development and its dysbiosis may signal pathological alterations that can be therapeutically targeted for regenerative medicine. In the end, we identify innovative research avenues that will merit from collaborations across biomedical disciplines that may facilitate the development of gut microbiome-based biomarkers and therapeutics. Gut microbiome stands as a core research area that transcends pediatric and nursing care, cancer biology, neurodegenerative disorders, cardiac function and diseases, among many other basic science and clinical arenas.
Publisher: SAGE Publications
Date: 11-2010
Abstract: If the rapidly progressing field of stem cell research reaches its full potential, successful treatments and enhanced understanding of many diseases are the likely results. However, the full potential of stem cell science will only be reached if all possible avenues can be explored and on a worldwide scale. Until 2009, the US had a highly restrictive policy on obtaining cells from human embryos and fetal tissue, a policy that pushed research toward the use of adult-derived cells. Currently, US policy is still in flux, and retrospective analysis does show the US lagging behind the rest of the world in the proportional increase in embryonic/fetal stem cell research. The majority of US studies being on either a limited number of cell lines, or on cells derived elsewhere (or funded by other sources than Federal) rather than on freshly isolated embryonic or fetal material. Neural, mesenchymal, and the mixed stem cell mononuclear fraction are the most commonly investigated types, which can generally be classified as adult-derived stem cells, although roughly half of the neural stem cells are fetal derived. Other types, such as embryonic and fat-derived stem cells, are increasing in their prominence, suggesting that new types of stem cells are still being pursued. Sixty percent of the reported stem cell studies involved transplantation, of which over three quarters were allogeneic transplants. A high proportion of the cardiovascular systems articles were on allogeneic transplants in a number of different species, including several autologous studies. A number of pharmaceutical grade stem cell products have also recently been tested and reported on. Stem cell research shows considerable promise for the treatment of a number of disorders, some of which have entered clinical trials over the next few years it will be interesting to see how these treatments progress in the clinic.
Publisher: Springer International Publishing
Date: 2016
DOI: 10.1007/978-3-319-45457-3_9
Abstract: Accumulating evidence has demonstrated that menstrual blood stands as a viable source of stem cells. Menstrual blood-derived stem cells (MenSCs) are morphologically and functionally similar to cells directly extracted from the endometrium, and present dual expression of mesenchymal and embryonic cell markers, thus becoming interesting tools for regenerative medicine. Functional reports show higher proliferative and self-renewal capacities than bone marrow-derived stem cells, as well as successful differentiation into hepatocyte-like cells, glial-like cells, endometrial stroma-like cells, among others. Moreover, menstrual blood stem cells may be used with increased efficiency in reprogramming techniques for induced Pluripotent Stem cell (iPS) generation. Experimental studies have shown successful treatment of stroke, colitis, limb ischemia, coronary disease, Duchenne's muscular atrophy and streptozotocin-induced type 1 diabetes animal models with MenSCs. As we envision an off-the-shelf product for cell therapy, cryopreserved MenSCs appear as a feasible clinical product. Clinical applications, although still very limited, have great potential and ongoing studies should be disclosed in the near future.
Publisher: Springer Science and Business Media LLC
Date: 10-10-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2011
DOI: 10.1161/STROKEAHA.110.601914
Abstract: Cell-based therapies represent a new therapeutic approach for stroke. In 2007, investigators from academia, industry leaders, and members of the National Institutes of Health crafted recommendations to facilitate the translational development of cellular therapies as a novel, emerging modality for stroke from animal studies to clinical trials. This meeting was called Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) and was modeled on the format of the Stroke Therapy Academic Industry Roundtable (STAIR) meetings. Since publication of the original STEPS guidelines, there has been an explosive growth in the number of cellular products and in the number of new laboratory discoveries that impact the safety and potential efficacy of cell therapies for stroke. Any successful development of a cell product will need to take into consideration several factors, including the preclinical safety and efficacy profile, cell characterization, delivery route, in vivo biodistribution, and mechanism of action. In 2010, a second meeting called STEPS 2 was held to bring together clinical and basic science researchers with industry, regulatory, and National Institutes of Health representatives. At this meeting, participants identified critical gaps in knowledge and research areas that require further studies, updated prior guidelines, and drafted new recommendations to create a framework to guide future investigations in cell-based therapies for stroke.
Publisher: SAGE Publications
Date: 30-06-2017
Publisher: Bentham Science Publishers Ltd.
Date: 2008
Publisher: SAGE Publications
Date: 05-2014
Abstract: Ischemic brain injury in adults and neonates is a significant clinical problem with limited therapeutic interventions. Currently, clinicians have only tPA available for stroke treatment and hypothermia for cerebral palsy. Owing to the lack of treatment options, there is a need for novel treatments such as stem cell therapy. Various stem cells including cells from embryo, fetus, perinatal, and adult tissues have proved effective in preclinical and small clinical trials. However, a limiting factor in the success of these treatments is the delivery of the cells and their by-products (neurotrophic factors) into the injured brain. We have demonstrated that mannitol, a drug with the potential to transiently open the blood–brain barrier and facilitate the entry of stem cells and trophic factors, as a solution to the delivery problem. The combination of stem cell therapy and mannitol may improve therapeutic outcomes in adult stroke and neonatal cerebral palsy.
Publisher: SAGE Publications
Date: 02-2018
Abstract: Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version “Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)”. The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Mary Ann Liebert Inc
Date: 02-2010
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.JCYT.2014.01.415
Abstract: We hypothesized that paracrine factors from human umbilical cord blood mononuclear cells (hUCBC) activate in injured cardiomyocytes the survival protein kinase Akt and limit activation of death protein kinases JNK and p38. We treated hUCBC with H2O2 and measured growth factors and cytokines secreted by hUCBC. We then treated cardiomyocytes with H2O2 for 24 h and measured Akt, JNK and p38 activation by means of Western blots. We also measured myocyte viability and apoptosis with the use of fluorescence-activated cell-sorting cytometry. We then investigated myocytes treated for 24 h with H2O2 plus hUCBC and myocytes without hUCBC or H2O2. Four million hUCBC were placed in transwells permeable only to hUCBC paracrine factors, and the transwells were placed in flasks with H2O2 + Dulbecco's modified Eagle's medium or in flasks with myocytes plus H2O2+Dulbecco's modified Eagle's medium. hUCBC increased secretion during H2O2 of hepatocyte growth factor by 338%, insulin-like growth factor by 200%, interleukin-4 by 200%, vascular endothelial cell growth factor by 192%, placental growth factor by 150%, interleukin-10 by 150% and angiogenin by 121%. H2O2 increased myocyte JNK activation by 237% and p38 activation by 60%, decreased myocyte viability by 38% and increased necrosis by 34% (all P 35%, increased viability by > 22% and decreased apoptosis by > 33% (all P < 0.05). Akt inhibitor API-1 prevented the effects of hUCBC and enhanced H2O2 decrease of myocyte viability. Addition of JNK inhibitor SP600125 or p38 inhibitor SB203580 to myocytes plus H2O2 prevented H2O2 decrease in viability and increased hUCBC beneficial effects. During free radical stress, hUCBC paracrine factors activate myocyte Akt, which increases myocyte viability by decreasing activation of death-promoting protein kinases JNK and p38.
Publisher: Wiley
Date: 31-05-2019
DOI: 10.1111/JCMM.14429
Abstract: Current therapies for Parkinson's disease (PD), including L‐3,4‐dihydroxyphenylalanine (L‐DOPA), and clinical trials investigating dopaminergic cell transplants, have generated mixed results with the eventual induction of dyskinetic side effects. Although human umbilical cord blood (hUCB) stem rogenitor cells present with no or minimal capacity of differentiation into mature dopaminergic neurons, their transplantation significantly attenuates parkinsonian symptoms likely via bystander effects, specifically stem cell graft‐mediated secretion of growth factors, anti‐inflammatory cytokines, or synaptic function altogether promoting brain repair. Recognizing this non‐cell replacement mechanism, we examined here the effects of intravenously transplanted combination of hUCB‐derived plasma into the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced rat model of PD. Animals received repeated dosing of either hUCB‐derived plasma or vehicle at 3, 5 and 10 days after induction into MPTP lesion, then behaviourally and immunohistochemically evaluated over 56 days post‐lesion. Compared to vehicle treatment, transplantation with hUCB‐derived plasma significantly improved motor function, gut motility and dopaminergic neuronal survival in the substantia nigra pars compacta (SNpc), which coincided with reduced pro‐inflammatory cytokines in both the SNpc and the intestinal mucosa and d ened inflammation‐associated gut microbiota. These novel data directly implicate a key pathological crosstalk between gut and brain ushering a new avenue of therapeutically targeting the gut microbiome with hUCB‐derived stem cells and plasma for PD.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.BRAINRES.2011.04.049
Abstract: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with a complicated pathogenesis. Compelling evidence indicates impairment of all neurovascular unit components including the blood-brain and blood-spinal cord barriers (BBB/BSCB) in both patients and animal models, leading to classification of ALS as a neurovascular disease. The present review provides an updated analysis of the normal and impaired BBB/BSCB, focusing on the ALS-altered barrier. Here we describe the roles of cellular components, tight junctions, transport systems, cell interactions, cytokines, matrix metalloproteinases, and free radicals in the BBB/BSCB disruption, along with recent evidence from experimental and clinical ALS studies. The BBB/BSCB is a promising research area in ALS and this review will reveal some aspects of microvascular pathology in ALS and hopefully provide ideas for the development of new therapeutic strategies.
Publisher: SAGE Publications
Date: 03-2015
Abstract: Traumatic brain injury (TBI), a major contributor to deaths and permanent disability worldwide, has been recently described as a progressive cell death process rather than an acute event. TBI pathophysiology is complicated and can be distinguished by the initial primary injury and the subsequent secondary injury that ensues days after the trauma. Therapeutic opportunities for TBI remain very limited with patients subjected to surgery or rehabilitation therapy. The efficacy of stem cell-based interventions, as well as neuroprotective agents in other neurological disorders of which pathologies overlap with TBI, indicates their potential as alternative TBI treatments. Furthermore, their therapeutic limitations may be augmented when combination therapy is pursued instead of using a single agent. Indeed, we demonstrated remarkable combined efficacy of human umbilical cord blood (hUCB) cell therapy and granulocyte-colony-stimulating factor (G-CSF) treatment in TBI models, providing essential evidence for the translation of this approach to treat TBI. Further studies are warranted to determine the mechanisms underlying therapeutic benefits exerted by hUCB + G-CSF in order to enhance its safety and efficacy in the clinic.
Publisher: Bentham Science Publishers Ltd.
Date: 12-2009
DOI: 10.2174/156720509790147115
Abstract: Inhibition of beta-amyloid (A beta) accumulation and A beta fibril (fA beta) formation from A beta are attractive therapeutic targets for the treatment of Alzheimer's disease (AD). While previous studies have shown anti-amyloidogenic effects of curcumin in vitro and in vivo, no studies have examined optimized turmeric extracts enriched in curcuminoids or turmerones. Three standardized turmeric extracts, HSS-838, HSS-848, and HSS-888, were prepared with different chemical profiles to investigate their potential therapeutic benefits for AD. These extracts were fingerprinted by DART TOF-MS to reveal the significant chemical complexity. In addition four curcuminoids (curcumin, tetrahydrocurcumin, demethoxycurcumin and bisdemethoxycurcumin) were also examined. We measured the effects of the extracts and curcuminoids, on the aggregation of A beta by using a thioflavin T cell-free assay and the secretion of A beta from human neuronal cells (SweAPP N2A cells) in vitro. All three extracts and the curcuminoids showed dose-dependent inhibition of fA beta aggregation from A beta(1-42) in the cell-free assay, with IC(50) values of <or= 5 microg/mL. However, only HSS-888, curcumin and demethoxycurcumin significantly decreased A beta secretion (approximately 20%) in SweAPP N2A cells. Interaction matrices were used to examine possible synergistic interactions between HS-888 and the other extracts and the in idual curcuminoids on A beta aggregation. Only simple additive effects were observed for the A beta aggregation inhibition, supporting the notion that the known curcuminoids are not strong inhibitors of this activity. However, HSS-888 showed strong inhibition of A beta aggregation and secretion, thus indicating that there are novel bioactive molecules in this extract that might be important leads for future AD drug discovery efforts.
Publisher: Public Library of Science (PLoS)
Date: 07-03-2011
Publisher: SAGE Publications
Date: 28-05-2019
Abstract: Returning veterans are frequently diagnosed with traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Considering a recent case-controlled study of hyperbaric oxygen therapy (HBOT) reporting a reduction in suicidal ideation, we investigated retrospectively three veterans with chronic TBI/PTSD symptoms who were treated with multiple rounds of HBOT with neurophysiological testing performed before and after treatment. Improvements were detected on parameters within neurocognitive domains, including reductions in suicide-related symptoms. These findings independently confirm that HBOT may be effective in treating specific symptoms of TBI/PTSD that are not currently addressed with existing therapeutic approaches.
Publisher: Elsevier BV
Date: 30-10-2009
DOI: 10.1016/J.JNEUROIM.2009.07.011
Abstract: In ALS, evidence suggests immune reactions in disease pathogenesis. Although immunological changes point to adaptive immune response, whether humoral or cellular response dominates during disease course is unknown. The study aim was to evaluate humoral immune response in ALS patients during disease progression. Circulating immune complexes (CICs), IgG, and IgM in sera of ALS patients and matching controls were evaluated after each of two visits. Results showed significantly elevated CICs and IgG in ALS patient sera. CICs decreased to control levels at the second visit, yet IgG remained higher than controls. Serum IgM was within normal range. Results suggest a humoral immune response initiating adaptive immunity in ALS, however, cellular immune response needs verification.
Publisher: Springer Science and Business Media LLC
Date: 17-07-2019
DOI: 10.1007/S12015-019-09906-2
Abstract: Pharmaceuticals and cell-based regenerative medicine for Parkinson’s disease (PD) offer palliative relief but do not arrest the disease progression. Cell therapy has emerged as an experimental treatment, but current cell sources such as human umbilical cord blood (hUCB) stem cells display only partial recapitulation of mature dopaminergic neuron phenotype and function. Nonetheless, stem cell grafts ameliorate PD-associated histological and behavioral deficits likely through stem cell graft-secreted therapeutic substances. We recently demonstrated the potential of hUCB-derived plasma in enhancing motor capabilities and gastrointestinal function, as well as preventing dopaminergic neuronal cell loss, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) rodent model of PD. Recognizing the translational need to test in another PD model, we now examined here the effects of an intravenously transplanted combination of hUCB and plasma into the 6-hydroxydopamine (6-OHDA) lesioned adult rats. Animals received three separate doses of 4 × 10 6 hUCB cells with plasma beginning at 7 days after stereotaxic 6-OHDA lesion, then behaviorally and immunohistochemically evaluated over 56 days post-lesion. Whereas vehicle-treated lesioned animals exhibited the typical 6-OHDA neurobehavioral symptoms, hUCB and plasma-treated lesioned animals showed significant attenuation of motor function, gut motility, and nigral dopaminergic neuronal survival, combined with diminished pro-inflammatory microbiomes not only in the nigra, but also in the gut. Altogether these data support a regenerative medicine approach for PD by sequestering inflammation and neurotoxicity through correction of gut dysbiosis.
Publisher: Mary Ann Liebert Inc
Date: 02-2013
Publisher: SAGE Publications
Date: 04-2015
Abstract: We propose that stem cell therapy may be a potent treatment for metastatic melanoma in the brain. Here we discuss the key role of a leaky blood-brain barrier (BBB) that accompanies the development of brain metastases. We review the need to characterize the immunological and inflammatory responses associated with tumor-derived BBB damage in order to reveal the contribution of this brain pathological alteration to the formation and growth of brain metastatic cancers. Next, we discuss the potential repair of the BBB and attenuation of brain metastasis through transplantation of bone marrow-derived mesenchymal stem cells with the endothelial progenitor cell phenotype. In particular, we review the need for evaluation of the efficacy of stem cell therapy in repairing a disrupted BBB in an effort to reduce neuroinflammation, eventually attenuating brain metastatic cancers. The demonstration of BBB repair through augmented angiogenesis and vasculogenesis will be critical to establishing the potential of stem cell therapy for the treatment revention of metastatic brain tumors. The overarching hypothesis we advanced here is that BBB breakdown is closely associated with brain metastatic cancers of melanoma, exacerbating the inflammatory response of the brain during metastasis, and ultimately worsening the outcome of metastatic brain cancers. Abrogating this leaky BBB-mediated inflammation via stem cell therapy represents a paradigm-shifting approach to treating brain cancer. This review article discusses the pros and cons of cell therapy for melanoma brain metastases.
Publisher: Elsevier BV
Date: 12-2012
Publisher: Elsevier
Date: 2007
Publisher: Springer Science and Business Media LLC
Date: 04-09-2012
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.JNEUROIM.2013.09.020
Abstract: Neurodegenerative diseases affect a considerable percentage of the elderly population. New therapeutic approaches are warranted, aiming to at least delay and possibly reverse disease progression. Strategies to elaborate such approaches require knowledge of specific immune system involvement in disease pathogenesis. In this review, innate and adaptive immunological aspects of neurodegenerative disorders, in particular Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS), are discussed. Initiating disease factors, as well as common mechanistic pathways, are detailed and potential immunological therapeutic targets are identified.
Publisher: Mary Ann Liebert Inc
Date: 02-2008
Abstract: This study examined whether dietary supplementation can be used to protect against ischemic stroke. Two groups of adult male Sprague-Dawley rats initially received NT-020, a proprietary formulation of blueberry, green tea, Vitamin D3, and carnosine (n = 8), or vehicle (n = 7). Dosing for NT-020 and vehicle consisted of daily oral administration (using a gavage) over a 2-week period. On day 14 following the last drug treatment, all animals underwent the stroke surgery using the transient 1-hour suture occlusion of middle cerebral artery (MCAo). To reveal the functional effects of NT-020, animals were subjected to established behavioral tests just prior to stroke surgery and again on day 14 post-stroke. ANOVA revealed significant treatment effects (p < 0.05), characterized by reductions of 11.8% and 24.4% in motor asymmetry and neurologic dysfunction, respectively, in NT-020-treated stroke animals compared to vehicle-treated stroke animals. Evaluation of cerebral infarction revealed a significant 75% decrement in mean glial scar area in the ischemic striatum of NT-020-treated stroke animals compared to that of vehicle-treated stroke animals (p < 0.0005). Quantitative analysis of subventricular zone's cell proliferative activity revealed at least a one-fold increment in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0005). Similarly, quantitative analysis of BrdU labeling in the ischemic striatal penumbra revealed at least a three-fold increase in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0001). In addition, widespread double labeling of cells with BrdU and doublecortin was detected in NT-020-treated stroke brains (intact side 17% and ischemic side 75%), which was significantly higher than those seen in vehicle-treated stroke brains (intact side 5% and ischemic side 13%) (p < 0.05). In contrast, only a small number of cells in NT-020-treated stroke brains double labeled with BrdU and GFAP (intact side 1% and ischemic side 2%), which was significantly lower than those vehicle-treated stroke brains (intact side 18% and ischemic side 35%) (p < 0.0001). Endogenous neurogenic factors were also significantly upregulated in the ischemic brains of NT-020-treated stroke animals. These data demonstrate the remarkable neuroprotective effects of NT-020 when given prior to stroke, possibly acting via its neurogenic potential.
Publisher: Mary Ann Liebert Inc
Date: 04-2010
Publisher: Proceedings of the National Academy of Sciences
Date: 28-07-2009
Abstract: The clinical evaluation of neural transplantation as a potential treatment for Huntington's disease (HD) was initiated in an attempt to replace lost neurons and improve patient outcomes. Two of 3 patients with HD reported here, who underwent neural transplantation containing striatal anlagen in the striatum a decade earlier, have demonstrated marginal and transient clinical benefits. Their brains were evaluated immunohistochemically and with electron microscopy for markers of projection neurons and interneurons, inflammatory cells, abnormal huntingtin protein, and host-derived connectivity. Surviving grafts were identified bilaterally in 2 of the subjects and displayed classic striatal projection neurons and interneurons. Genetic markers of HD were not expressed within the graft. Here we report in patients with HD that ( i ) graft survival is attenuated long-term ( ii ) grafts undergo disease-like neuronal degeneration with a preferential loss of projection neurons in comparison to interneurons ( iii ) immunologically unrelated cells degenerate more rapidly than the patient's neurons, particularly the projection neuron subtype ( iv ) graft survival is attenuated in the caudate in comparison to the putamen in HD ( v ) glutamatergic cortical neurons project to transplanted striatal neurons and ( vi ) microglial inflammatory changes in the grafts specifically target the neuronal components of the grafts. These results, when combined, raise uncertainty about this potential therapeutic approach for the treatment of HD. However, these observations provide new opportunities to investigate the underlying mechanisms involved in HD, as well as to explore additional therapeutic paradigms.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3RA46962J
Abstract: Despite its narrow therapeutic window, lithium is still regarded as the gold standard comparator and benchmark treatment for mania.
Publisher: Springer Science and Business Media LLC
Date: 18-12-2009
DOI: 10.1007/S12015-009-9108-7
Abstract: Autologous transplantation of stem cells is a natural phenomenon at birth in mammals via the umbilical cord. Here, we discuss that a delay in the cord cl ing may increase stem cell supply to the baby, thereby allowing an innate stem cell therapy that can render acute benefits in the case of neonatal disease, as well as long-term benefits against age-related diseases.
Publisher: Elsevier BV
Date: 03-2014
Publisher: Mary Ann Liebert Inc
Date: 06-2008
Publisher: SAGE Publications
Date: 09-2007
DOI: 10.3727/000000007783465190
Abstract: One of the fastest growing fields in researching treatments for neurodegenerative and other disorders is the use of stem cells. These cells are naturally occurring and can be obtained from three different stages of an organism's life: embryonic, fetal, and adult. In the US, political doctrine has restricted use of federal funds for stem cells, enhancing research towards an adult source. In order to determine how this legislation may be represented by the stem cell field, a retrospective analysis of stem cell articles published in the journal Cell Transplantation over a 2-year period was performed. Cell Transplantation is considered a translational journal from preclinical to clinical, so it was of interest to determine the publication outcome of stem cell articles 6 years after the US regulations. The distribution of the source of stem cells was found to be biased towards the adult stage, but relatively similar over the embryonic and fetal stages. The fetal stem cell reports were primarily neural in origin, whereas the adult stem cell ones were predominantly mesenchymal and used mainly in neural studies. The majority of stem cell studies published in Cell Transplantation were found to fall under the umbrella of neuroscience research. American scientists published the most articles using stem cells with a bias towards adult stem cells, supporting the effect of the legislation, whereas Europe was the leading continent with a bias towards embryonic and fetal stem cells, where research is “controlled” but not restricted. Japan was also a major player in the use of stem cells. Allogeneic transplants (where donor and recipient are the same species) were the most common transplants recorded, although the transplantation of human-derived stem cells into rodents was the most common specific transplantation performed. This demonstrates that the use of stem cells is an increasingly important field (with a doubling of papers between 2005 and 2006), which is likely to develop into a major therapeutic area over the next few decades and that funding restrictions can affect the type of research being performed.
Publisher: Public Library of Science (PLoS)
Date: 12-03-2014
Publisher: MDPI AG
Date: 31-01-2018
DOI: 10.3390/IJMS19020423
Publisher: MDPI AG
Date: 09-01-2014
DOI: 10.3390/IJMS15010895
Publisher: Springer Science and Business Media LLC
Date: 09-2008
DOI: 10.1007/BF03033511
Publisher: SAGE Publications
Date: 2016
Abstract: Human umbilical cord blood cells (HUCBCs), a prolific source of non-embryonic or adult stem cells, have emerged as effective and relatively safe immunomodulators and neuroprotectors, reducing behavioral impairment in animal models of Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and stroke. In this report, we followed the bioavailability of HUCBCs in AD-like transgenic PSAPP mice and nontransgenic Sprague-Dawley rats. HUCBCs were injected into tail veins of mice or rats at a single dose of 1 × 10 6 or 2.2 × 10 6 cells, respectively, prior to harvesting of tissues at 24 h, 7 days, and 30 days after injection. For determination of HUCBC distribution, tissues from both species were subjected to total DNA isolation and polymerase chain reaction (PCR) lification of the gene for human glycerol-3-phosphate dehydrogenase. Our results show a relatively similar biodistribution and retention of HUCBCs in both mouse and rat organs. HUCBCs were broadly detected both in the brain and several peripheral organs, including the liver, kidney, and bone marrow, of both species, starting within 7 days and continuing up to 30 days posttransplantation. No HUCBCs were recovered in the peripheral circulation, even at 24 h posttransplantation. Therefore, HUCBCs reach several tissues including the brain following a single intravenous treatment, suggesting that this route can be a viable method of administration of these cells for the treatment of neurodegenerative diseases.
Publisher: Springer Science and Business Media LLC
Date: 2015
DOI: 10.1038/517438C
Publisher: Wiley
Date: 02-2010
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.NEUBIOREV.2011.05.010
Abstract: Cerebrovascular diseases are the third leading cause of death and the primary cause of long-term disability in the United States. The only approved therapy for stroke is tPA, strongly limited by the short therapeutic window and hemorrhagic complications, therefore excluding most patients from its benefits. Parkinson's and Huntington's disease are the other two most studied basal ganglia diseases and, as stroke, have very limited treatment options. Inflammation is a key feature in central nervous system disorders and it plays a dual role, either improving injury in early phases or impairing neural survival at later stages. Stem cells can be opportunely used to modulate inflammation, abrogate cell death and, therefore, preserve neural function. We here discuss the role of stem cells as restorative treatments for basal ganglia disorders, including Parkinson's disease, Huntington's disease and stroke, with special emphasis to the recently investigated menstrual blood stem cells. We highlight the availability, proliferative capacity, pluripotentiality and angiogenic features of these cells and explore their present and future experimental and clinical applications.
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.BRAINRES.2009.06.067
Abstract: The clinical presentation of traumatic brain injury (TBI) involves either mild, moderate, or severe injury to the head resulting in long-term and even permanent disability. The recapitulation of this clinical scenario in animal models should allow examination of the pathophysiology of the trauma and its treatment. To date, only a few studies have demonstrated TBI animal models encompassing the three levels of trauma severity. Thus, in the present study we characterized in mice and rats both brain histopathologic and behavioral alterations across a range of injury magnitudes arising from mild, moderate, and severe TBI produced by controlled cortical impact injury technique. Here, we replicated the previously observed TBI severity-dependent brain damage as revealed by 2,3,5-triphenyltetrazolium chloride staining (severe > moderate > mild) in rats, but also extended this pattern of histopathologic changes in mice. Moreover, we showed severity-dependent abnormalities in locomotor and cognitive behaviors in TBI-exposed rats and mice. Taken together, these results support the use of rodent models of TBI as a sensitive platform for investigations of the injury-induced neurostructural and behavioral deficits, which should serve as key outcome parameters for testing experimental therapeutics.
Publisher: Humana Press
Date: 2009
DOI: 10.1007/978-1-60327-931-4_9
Abstract: The umbilical cord of a healthy neonate contains within it a multipotential treatment for a myriad of diseases and injuries. What was once tossed into the biohazard waste without a second thought is now known to be a goldmine of antigenically immature cells that rival the use of bone marrow for reconstitution of blood lineages. Umbilical cord blood (UCB) is emerging as an effective and feasible clinical treatment as its availability increases and benefits are realized. Basic science research has demonstrated a broad therapeutic capacity ranging from cell replacement to cell protection and anti-inflammation in a number of animal disease and injury models. UCB is easily obtained with no harm to infant or mother and can be stored at cryogenic temperatures with relatively little loss of cells upon thaw. The heterogeneous mononuclear fraction has been identified and characterized and transplanted both locally and systemically to treat animal models of stroke, myocardial infarction, Amytrophic Lateral Sclerosis, San Filippo, spinal cord injury, traumatic brain injury, and age-related neurodegeneration, among others. In the pages to follow, we share protocols for the identification and research use of the mononuclear cell fraction of UCB.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Wiley
Date: 28-01-2015
DOI: 10.1002/JCP.24830
Publisher: Humana Press
Date: 2011
Publisher: SAGE Publications
Date: 12-2014
Abstract: Sanfilippo syndrome type III B (MPS III B) is an inherited disorder characterized by a deficiency of α- N-acetylglucosaminidase (Naglu) enzyme leading to accumulation of heparan sulfate in lysosomes and severe neurological deficits. We have previously shown that a single administration of human umbilical cord mononuclear cells (hUCB MNCs) into Naglu knockout mice decreased behavioral abnormalities and tissue pathology. In this study, we tested whether repeated doses of hUCB MNCs would be more beneficial than a single dose of cells. Naglu mice at 3 months of age were randomly assigned to either a Media-only group or one of three hUCB MNC treatment groups-single low dose (3 × 10 6 cells), single high dose (1.8 × 10 7 cells), or multiple doses (3 × 10 6 cells monthly for 6 months) delivered intravenously cyclosporine was injected intraperitoneally to immune suppress the mice for the duration of the study. An additional control group of wild-type mice was also used. We measured anxiety in an open field test and cognition in an active avoidance test prior to treatment and then at monthly intervals for 6 months. hUCB MNCs restored normal anxiety-like behavior in these mice ( p 0.001). The repeated cell administrations also restored hippoc al cytoarchitecture, protected the dendritic tree, decreased GM3 ganglioside accumulation, and decreased microglial activation, particularly in the hippoc us and cortex. These data suggest that the neuroprotective effect of hUCB MNCs can be enhanced by repeated cell administrations.
Publisher: Wiley
Date: 10-07-2013
DOI: 10.1002/GLIA.22544
Publisher: Informa UK Limited
Date: 2008
DOI: 10.1080/17482960802160990
Abstract: Our letter to the editor addresses important questions regarding the role of the blood-spinal cord barrier in amyotrophic lateral sclerosis. The novel finding of barrier dysfunction in ALS has implications for disease pathogenesis. This discussion should prove of widespread interest to researchers and may help in formulating various new therapeutic strategies to protect barrier function and thus extend functionality and lifespan in ALS patients.
Publisher: Springer Science and Business Media LLC
Date: 20-08-2020
Publisher: SAGE Publications
Date: 08-2016
Abstract: Despite the high prevalence and devastating outcome, there remain a few options for treatment of ischemic stroke. Currently available treatments are limited by a short time window for treatment and marginal efficacy when used. We have tested a human umbilical cord blood-derived stem cell line that has been shown to result in a significant reduction in stroke infarct volume as well as improved functional recovery following stroke in the rat. In the present study we address the mechanism of action and compared the therapeutic efficacy of high- versus low-passage nonhematopoietic umbilical cord blood stem cells (nh-UCBSCs). Using the middle cerebral arterial occlusion (MCAo) model of stroke in Sprague–Dawley rats, we administered nh-UCBSC by intravenous (IV) injection 2 days following stroke induction. These human cells were injected into rats without any immune suppression, and no adverse reactions were detected. Both behavioral and histological analyses have shown that the administration of these cells reduces the infarct volume by 50% as well as improves the functional outcome of these rats following stroke for both high- and low-passaged nh-UCBSCs. Flow cytometry analysis of immune cells present in the brains of normal rats, rats with ischemic brain injury, and ischemic animals with nh-UCBSC treatment confirmed infiltration of macrophages and T cells consequent to ischemia and reduction to normal levels with nh-UCBSC treatment. Flow cytometry also revealed a restoration of normal levels of microglia in the brain following treatment. These data suggest that nh-UCBSCs may act by inhibiting immune cell migration into the brain from the periphery and possibly by inhibition of immune cell activation within the brain. nh-UCBSCs exhibit great potential for treatment of stroke, including the fact that they are associated with an increased therapeutic time window, no known ill-effects, and that they can be expanded to high numbers for, and stored for, treatment.
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.LFS.2007.05.025
Abstract: Human NT cells derived from the NTera2/D1 cell line express a dopaminergic phenotype making them an attractive vehicle to supply dopamine to the depleted striatum of the Parkinsonian patient. In vitro, hNT neurons express tyrosine hydroxylase (TH), depending on the length of time they are exposed to retinoic acid. This study compared two populations of hNT neurons that exhibit a high yield of TH+ cells, MI-hNT and DA-hNT. The MI-hNT and DA-hNT neurons were intrastriatally transplanted into the 6-OHDA hemiparkinsonian rat. Amelioration in rotational behavior was measured and immunohistochemistry was performed to identify surviving hNT and TH+ hNT neurons. Results indicated that both MI-hNT and DA-hNT neurons can survive in the striatum, however, neither maintained their dopaminergic phenotype in vivo. Other strategies used in conjunction with hNT cell replacement are likely needed to enhance and maintain the dopamine expression in the grafted cells.
Publisher: Elsevier BV
Date: 12-2018
Publisher: Future Medicine Ltd
Date: 07-2007
Abstract: One of the most promising treatments for neurodegenerative diseases appears to be human umbilical cord blood cell transplantation. A variety of studies demonstrate some benefit of this method of treatment in a number of different animal models and case studies. However, before the methodologies and results of these animal studies and case studies can be translated into successful widespread treatments, aspects relating to the immunological properties of the transplanted cells must be considered. In this perspective, we discuss the benefit of the cellular immaturity of these cells with respect to the immune response, and compare cord blood transplantation to blood transfusions, as well as discussing what future studies should entail.
Publisher: Public Library of Science (PLoS)
Date: 20-09-2012
Publisher: Elsevier BV
Date: 05-2019
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.BRAINRES.2007.04.044
Abstract: The purpose of this study was to determine the ultrastructure of the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) in G93A SOD1 mice modeling ALS at different stages of disease. Electron microscope examination of brainstem, cervical and lumbar spinal cords was performed in ALS mice at early and late stages of disease. Our results show disorganized mitochondrial cristae and degenerating mitochondria in endothelial cells and neuropil, swollen astrocyte foot processes, swollen and degenerating capillary endothelial cells, astrocytes and motor neurons and extensive extracellular edema. In spite of progressive extracellular edema in neural tissue, capillary endothelial cell tight junctions appeared to remain intact in early and late symptomatic animals. Results show that disruption of BBB and BSCB was evident in areas of motor neuron degeneration in G93A mice at both early and late stages of disease. Capillary rupture was observed in brainstem in early symptomatic G93A mice. Capillary ultrastructure revealed that endothelial cell membrane and/or basement membrane damage occurred, followed by vascular leakage.
Publisher: SAGE Publications
Date: 07-2025
DOI: 10.1177/09636897211049814
Abstract: During the past 18 months as the world dealt with the COVID-19 pandemic, articles published in Cell Transplantation ( CT) voiced unique perspectives on the disease which have since been supported by additional research. Intrigued by the variability in COVID-19 severity, CT authors explored the influence of variants in angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) genes, as well as the role of androgen receptors on disease development. Mesenchymal stem cells (MSC) were offered up as a potential COVID-19 therapy because of their immune modulating characteristics and successful use in other acute respiratory diseases. Two CT author groups gave proof of principle when hospitalized COVID-19 patients were infused with MSC after no other interventions seemed to work. MSC treatment reduced disease severity and shortened hospitalization stays. Lastly, CT authors speculated why we are still in the midst of a pandemic and the consequences of disillusioned comfort as we face new emerging variants that may undermine all we have accomplished thus far.
Publisher: SAGE Publications
Date: 12-2009
Abstract: Autologous bone marrow mononuclear cell (BMMC) transplantation has emerged as a potential therapeutic option for refractory angina patients. Previous studies have shown conflicting myocardium reperfusion results. The present study evaluated safety and efficacy of CellPraxis Refractory Angina Cell Therapy Protocol (ReACT), in which a specific BMMC formulation was administered as the sole therapy for these patients. The phase I/IIa noncontrolled, open label, clinical trial, involved eight patients with refractory angina and viable ischemic myocardium, without left ventricular dysfunction and who were not suitable for conventional myocardial revascularization. ReACT is a surgical procedure involving a single series of multiple injections (40–90 injections, 0.2 ml each) into ischemic areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at 18 months follow-up and myocardium ischemic area reduction (assessed by scintigraphic analysis) at 12 months follow-up, in correlation with a specific BMMC formulation. Almost all patients presented progressive improvement in angina classification beginning 3 months ( p = 0.008) postprocedure, which was sustained at 18 months follow-up ( p = 0.004), as well as objective myocardium ischemic area reduction at 12 months (decrease of 84.4%, p 0.004). A positive correlation was found between monocyte concentration and CCSAC improvement ( r = −0.759, p 0.05). Improvement in CCSAC, followed by correlated reduction in scintigraphic myocardium ischemic area, strongly suggests neoangiogenesis as the main stem cell action mechanism. The significant correlation between number of monocytes and improvement strongly supports a cell-related effect of ReACT. ReACT appeared safe and effective.
Publisher: SAGE Publications
Date: 2010
Publisher: Future Medicine Ltd
Date: 09-2019
Publisher: Elsevier BV
Date: 08-2019
Publisher: Mary Ann Liebert Inc
Date: 12-2008
Abstract: We investigated whether human umbilical cord blood mononuclear cells (HUCBC), which contain hematopoietic and mesenchymal progenitor cells, can limit myocardial cytokine expression and inflammatory cell infiltration in acute myocardial infarction. We permanently ligated the left coronary artery of rats and injected into the myocardium either Isolyte or 4 x 10(6) HUCBC in Isolyte and measured myocardial cytokines with antibody arrays at 2, 6, 12, 24, and 72 hours after infarction. We then measured with flow cytometry myocardial macrophages, neutrophils and lymphocytes at 12, 24, and 72 hours after infarctions in rats treated with either intramyocardial Isolyte or 4 x 10(6) HUCBC. In the Isolyte-treated hearts, between 2 and 12 hours after myocardial infarction, tumor necrosis factor-alpha increased from 6.7 +/- 0.9% to 52.3 +/- 4.7%, monocyte chemoattract protein increased from 9.5 +/- 1.2% to 39.8 +/- 2.1%, fractalkine increased from 11 +/- 1.5% to 28.1 +/- 1.3%, ciliary neurotrophic factor increased from 12.1 +/- 0.02% to 25.9 +/- 1.1%, macrophage inflammatory protein increased from 10.3 +/- 1.5% to 23.9.0 +/- 1.4%, interferon-gamma increased from 8.7 +/- 0.4% to 26.0 +/- 1.6%, interleukin-1beta increased from 6.1 +/- 0.04% to 19.0 +/- 1.2%, and IL-4 increased from 5.9 +/- 0.03% to 15 +/- 1.5% (all p < 0.001 compared with controls). The concentrations of fractalkine remained significantly increased at 72 hours after acute infarction. In contrast, the myocardial concentrations of these cytokines did not significantly change in HUCBC treated hearts at 2, 6, 12, 24, or 72 hours after infarction. The percentage of neutrophils increased from 0.04 +/- 0.2%/50,000 heart cells in the controls to 5.3 +/- 1.2%/50,000 heart cells 12 hours after infarction in Isolyte-treated hearts but averaged only 1.3 +/- 0.7%/50,000 heart cells in HUCBC treated hearts (p < 0.02). Thereafter, the percentages of neutrophils rapidly decreased at 24 and at 72 hours after infarction and averaged 0.6 +/- 0.2%/50,000 heart cells at 72 hours after infarction in Isolyte-treated hearts in contrast to 0.2 +/- 0.1%/50,000 cells in HUCBC hearts (p < 0.05). Moreover, the percentages of neutrophils at 24 and 72 hours in HUCBC hearts were not significantly different from controls. At 24 hours post infarction, the percentage of CD3 and CD4 lymphocytes were 10.7 +/- 1.4% and 6.3 +/- 1.1%/50,000 cells in Isolyte hearts in comparison with only 4.9 +/- 0.8% and 2.9 +/- 0.5% in HUCBC hearts (p < 0.005 for Isolyte versus HUCBC). The percentage of CD11b macrophages was 2.8 +/- 0.3% in Isolyte hearts and 1.9 +/- 0.2% in HUCBC treated hearts (p < 0.05). At 72 hours after infarction, the percentage of CD3 and CD4 lymphocytes averaged 8.0 +/- 1.1% and 5.1 +/- 0.8%/50,000 heart cells in Isolyte hearts in comparison with only 4.1 +/- 0.5% and 2.3 +/- 0.4%/50,000 heart cells in the HUCBC treated infarctions (p < 0.005). Left ventricular infarct sizes in Isolyte-treated hearts at 72 hours post infarction averaged 15.7 +/- 1.4% of the left ventricular muscle area in contrast to HUCBC treated infarctions that averaged 6.9 +/- 1.4% of the left ventricular muscle area (p < 0.02). Moreover in rats followed for 2 months post infarction, the LV ejection fractions decreased to 65.4 +/- 1.9% and 69.1 +/- 1.9% at 1 and 2 months after infarction in Isolyte-treated hearts and were significantly different from HUCBC treated hearts that averaged 72.1 +/- 1.3% and 75.7 +/- 1.4% (both p < 0.02). The present experiments suggest that an important mechanism whereby HUCBC limit infarct size and improve left ventricular ejection fraction is by significantly limiting inflammatory cytokines and inflammatory cells in infarcted myocardium.
Publisher: Mary Ann Liebert Inc
Date: 06-2007
Abstract: During natural aging, adult stem cells are known to have a reduced restorative capacity and are more vulnerable to oxidative stress resulting in a reduced ability of the body to heal itself. We report here that the proprietary natural product formulation, NT020, previously found to promote proliferation of human hematopoietic stem cells, reduced oxidative stress-induced apoptosis of murine neurons and microglial cells in vitro. Furthermore, when taken orally for 2 weeks, cultured bone marrow stem cells from these mice exhibited a dose-related reduction of oxidative stress-induced apoptosis. This preclinical study demonstrates that NT020 can act to promote healing via an interaction with stem cell populations and forms the basis of conducting a clinical trial to determine if NT020 exhibits similar health promoting effects in humans when used as a dietary supplement.
Publisher: Frontiers Media SA
Date: 2014
Publisher: Public Library of Science (PLoS)
Date: 09-12-2013
Publisher: Informa UK Limited
Date: 10-2016
DOI: 10.2147/NDT.S110126
Publisher: SAGE Publications
Date: 2021
DOI: 10.1177/09636897211053872
Abstract: The 28th American Society for Neural Therapy and Repair (ASNTR) returned to the Sheraton Sand Key in Clearwater Beach, Florida after an 18 month hiatus. Like nearly all conferences during the pandemic, the ASNTR conference was held in person while offering a virtual option to the event. These formats are advantageous for those under travel restrictions or personal constraints, but they lack the spontaneity of in-person connections. Highlights from the meeting included the return of the Bernard Sanberg Memorial Award and the Roy Bakay Memorial lecture. The presidential lecture was given by Gabriel de Erausquin, who discussed the possibility of long-term CNS effects resulting from SARS-CoV2 infection. With both virtual and in-person events, including oral and poster presentations, the ASNTR managed to maintain the unique essence of this small important meeting.
Start Date: 2015
End Date: 2021
Funder: Directorate for Computer & Information Science & Engineering
View Funded ActivityStart Date: 2018
End Date: 2021
Funder: Directorate for Computer & Information Science & Engineering
View Funded ActivityStart Date: 2009
End Date: 2010
Funder: Congressionally Directed Medical Research Programs
View Funded ActivityStart Date: 1994
End Date: 1998
Funder: National Institute of Neurological Disorders and Stroke
View Funded ActivityStart Date: 2010
End Date: 2011
Funder: National Institute of Neurological Disorders and Stroke
View Funded ActivityStart Date: 1984
End Date: 1985
Funder: National Institute of Mental Health
View Funded ActivityStart Date: 1988
End Date: 1992
Funder: National Institute of Neurological Disorders and Stroke
View Funded Activity