ORCID Profile
0000-0002-1913-6771
Current Organisations
University of Oxford
,
New York University
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Publisher: Hindawi Limited
Date: 07-08-2019
DOI: 10.1002/TERM.2947
Abstract: Bone marrow-derived mesenchymal stem/stromal cells (BMSCs) can differentiate into bone-forming osteoblasts, playing a crucial role in bone regeneration. Exosomes are naturally cell-secreted nanovesicles and are lately regraded as an emerging mediator of cellular communication in physiological and pathological conditions. The present study aimed at investigating the complex cellular communications, especially those among the differentiating BMSCs, immune cells (e.g., macrophages), and newly recruited BMSCs via exosome-mediated pathways. Exosomes were first isolated from osteogenically differentiating BMSCs at various stages (Day 0, Day 3, Day 7, and Day 14, respectively). The cellular uptake of isolated exosomes was examined in macrophages and human BMSCs (hBMSCs). The exosomes collected at various osteogenic differentiation stages (0d-exo, 3d-exo, 7d-exo, and 14d-exo) had no effect on the viability of hBMSCs. The uptake of exosomes (0d-exo, 3d-exo, and 7d-exo) significantly decreased proinflammatory-gene expression and the level of an M1 phenotypic marker. Our results then revealed that 3d-exo, 7d-exo, and 14d-exo led to a remarkable increase in mesenchymal stem/stromal cell migration. In addition, 0d-exo significantly promoted the expression of early osteogenic markers, such as alkaline phosphatase and bone morphogenetic protein 2, indicating a pro-osteogenic role of hBMSC-derived exosomes. Collectively, these results suggest that exosomes derived from differentiating mesenchymal stem/stromal cells play a unique osteoimmunomodulatory role in the regulation of bone dynamics.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.ACTBIO.2019.01.006
Abstract: Exosomes are extracellular nanovesicles that play an important role in cellular communication. The modulatory effects of bone morphogenetic protein 2 (BMP2) on macrophages have encouraged the functionalization of scaffolds through the integration of the exosomes from the BMP2-stimulated macrophages to avoid ectopic bone formation and reduce adverse effects. To determine the functionality of exosomal nanocarriers from macrophages after BMP2 stimulation, we isolated the exosomes from Dulbecco's modified Eagle's medium (DMEM)- or BMP2-stimulated macrophages and evaluated their effects on osteogenesis. Morphological characterization of the exosomes derived from DMEM- or BMP2-treated macrophages revealed no significant differences, and the bone marrow-derived mesenchymal stromal cells showed similar cellular uptake patterns for both exosomes. In vitro study using BMP2/macrophage-derived exosomes indicated their beneficial effects on osteogenic differentiation. To improve the bio-functionality for titanium implants, BMP2/macrophage-derived exosomes were used to modify titanium nanotube implants to favor osteogenesis. The incorporation of BMP2/macrophage-derived exosomes dramatically increased the expression of early osteoblastic differentiation markers, alkaline phosphatase (ALP) and BMP2, indicative of the pro-osteogenic role of the titanium nanotubes incorporated with BMP2/macrophage-derived exosomes. The titanium nanotubes functionalized with BMP2/macrophage-derived exosomes activated autophagy during osteogenic differentiation. In conclusion, the exosome-integrated titanium nanotube may serve as an emerging functional material for bone regeneration. STATEMENT OF SIGNIFICANCE: The clinical application of bone morphogenetic protein 2 (BMP2) is often limited by its side effects. Exosomes are naturally secreted nanosized vesicles derived from cells and play an important role in intercellular communication. The contributions of this study include (1) the demonstration of the potential regulatory role of BMP2/macrophage-derived exosomes on the osteogenic differentiation of mesenchymal stromal cells (MSCs) (2) fabrication of titanium nanotubes incorporated with exosomes (3) new insights into the application of titanium nanotube-based materials for the safe use of BMP2.
Publisher: Public Library of Science (PLoS)
Date: 20-09-2018
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.ACTBIO.2019.06.058
Abstract: Developing "osteoimmune-smart" bone substitute materials have become the forefront of research in bone regeneration. Biocompatible polymer coatings are applied widely to improve the bioactivity of bone substitute materials. In this context, polyoxazolines (Pox) have attracted substantial attention recently due to properties such as biocompatibility, stability, and low biofouling. In view of these useful properties, it is interesting to explore the capacity of Pox as an osteoimmunomodulatory agent to generate a favorable osteoimmune environment for osteogenesis. We applied a technique called plasma polymerization and succeeded in preparing Pox-like coatings (Ppox) and engineered their nanotopography at the nanoscale. We found that Ppox switched macrophages towards M2 extreme, thus inhibiting the release of inflammatory cytokines. The underlying mechanism may be related to the suppression of TLR pathway. The generated osteoimmune environment improved osteogenesis while inhibited osteoclastogenesis. This may be related to the release of osteogenic factors, especially Wnt10b from macrophages. The addition of nanotopography (16 nm, 38 nm, 68 nm) can tune the Ppox-mediated inhibition on inflammation and osteoclastic activities, while no significant effects were observed within the tested nano sizes on the Ppox-mediated osteogenesis. These results collectively suggest that Ppox can be useful as an effective osteoiumunomodulatory agent to endow bone substitute materials with favourable osteoimmunomodulatory property. STATEMENT OF SIGNIFICANCE: In this study, we succeeded in preparing plasma deposited Pox-like nano-coatings (Ppox) via plasma polymerization and found that Ppox nanotopographies are useful osteoimmunomodulatory tools. Their osteoimmunodolatory effects and underlying mechanisms are unveiled. It is the first investigation into the feasibility of applying poly-oxazoline as an osteoimmunomodulatory agent. This expand the application of poly-oxazoline into the forefront in bone regeneration area for the development of advanced "osteoimmune-smart" bone substitute materials.
Publisher: MDPI AG
Date: 06-04-2021
Abstract: Direct seeded rice (DSR) is a mainstay for planting rice in the Americas, and it is rapidly becoming more popular in Asia. It is essential to develop rice varieties that are suitable for this type of production system. ASD1, a landrace from India, possesses several traits desirable for direct-seeded fields, including tolerance to anaerobic germination (AG). To map the genetic basis of its tolerance, we examined a population of 200 F2:3 families derived from a cross between IR64 and ASD1 using the restriction site-associated DNA sequencing (RAD-seq) technology. This genotyping platform enabled the identification of 1921 single nucleotide polymorphism (SNP) markers to construct a high-resolution genetic linkage map with an average interval of 0.9 cM. Two significant quantitative trait loci (QTLs) were detected on chromosomes 7 and 9, qAG7 and qAG9, with LOD scores of 7.1 and 15.0 and R2 values of 15.1 and 29.4, respectively. Here, we obtained more precise locations of the QTLs than traditional simple sequence repeat and low-density SNP genotyping methods and may help further dissect the genetic factors of these QTLs.
Publisher: Public Library of Science (PLoS)
Date: 10-07-2014
Location: United Kingdom of Great Britain and Northern Ireland
Location: Germany
Location: Philippines
No related grants have been discovered for Maricris Zaidem.