ORCID Profile
0000-0001-8248-8190
Current Organisations
University of South Australia
,
The Ohio State University
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Publisher: American Chemical Society (ACS)
Date: 04-06-2021
Publisher: Research Square Platform LLC
Date: 07-08-2023
DOI: 10.21203/RS.3.RS-3204385/V1
Abstract: Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide abundantly expressed by corneal nerves. Using a murine model of corneal mechanical injury, we found CGRP levels in the cornea to be significantly reduced after injury. Topical application of CGRP as an eye drop accelerates corneal epithelial wound closure, reduces corneal opacification, and prevents corneal edema after injury in vivo. We then used a series of in vitro and in vivo techniques to investigate the mechanisms underlying CGRP’s functions. CGRP promotes corneal epithelial cell migration, proliferation, and the secretion of laminin. It reduces TGF-β1 signaling and prevents TGF-β1-mediated stromal fibroblast activation and tissue fibrosis. CGRP reduces corneal endothelial cell apoptosis, preserves cell density and morphology, and promotes their pump function, thus reducing edema. Lastly, CGRP reduces neutrophil infiltration, macrophage maturation, and the production of inflammatory cytokines in the cornea. Taken together, our results show that corneal nerve-derived CGRP plays a cyto-protective, pro-regenerative, anti-fibrotic, and anti-inflammatory role in corneal wound healing. Given that current treatment options for corneal injury and opacity are scarce, CGRP has significant therapeutic potential in this area of unmet medical needs. In addition, our results highlight the critical role of sensory nerves in ocular surface homeostasis and injury repair.
Publisher: Elsevier BV
Date: 07-2022
Publisher: Informa UK Limited
Date: 06-12-2019
Publisher: Oxford University Press (OUP)
Date: 13-02-2021
DOI: 10.1002/STEM.3351
Abstract: The interplay between mesenchymal stem cells (MSCs) and immune cells has been studied for MSCs isolated from different tissues. However, the immunomodulatory capacity of urine stem cells (USCs) has not been adequately researched. The present study reports on the effect of USCs on peripheral blood lymphocytes. USCs were isolated and characterized before coculture with resting and with anti-CD3/CD28 bead stimulated lymphocytes. Similarly to bone marrow mesenchymal stem cells (BM-MSCs), USCs inhibited the proliferation of activated T lymphocytes and induced their apoptosis. However, they also induced strong activation, proliferation, and cytokine and antibody production by B lymphocytes. Molecular phenotype and supernatant analysis revealed that USCs secrete a range of cytokines and effector molecules, known to play a central role in B cell biology. These included B cell-activating factor (BAFF), interleukin 6 (IL-6) and CD40L. These findings raise the possibility of an unrecognized active role for kidney stem cells in modulating local immune cells.
Publisher: MDPI AG
Date: 10-2015
Publisher: MDPI AG
Date: 05-01-2021
DOI: 10.3390/IJMS22010459
Abstract: Elucidation of the biological functions of extracellular vesicles (EVs) and their potential roles in physiological and pathological processes is an expanding field of research. In this study, we characterized USC–derived EVs and studied their capacity to modulate the human immune response in vitro. We found that the USC–derived EVs are a heterogeneous population, ranging in size from that of micro–vesicles (150 nm–1 μm) down to that of exosomes (60–150 nm). Regarding their immunomodulatory functions, we found that upon isolation, the EVs (60–150 nm) induced B cell proliferation and IgM antibody secretion. Analysis of the EV contents unexpectedly revealed the presence of BAFF, APRIL, IL–6, and CD40L, all known to play a central role in B cell stimulation, differentiation, and humoral immunity. In regard to their effect on T cell functions, they resembled the function of mesenchymal stem cell (MSC)–derived EVs previously described, suppressing T cell response to activation. The finding that USC–derived EVs transport a potent bioactive cargo opens the door to a novel therapeutic avenue for boosting B cell responses in immunodeficiency or cancer.
No related grants have been discovered for Asmaa Zidan.