期刊
CELLS
卷 11, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/cells11172696
关键词
mesenchymal stem; stromal cells; bone micro-computed; diabetes; inflammation; injury; fracture healing; starvation tomography (mu CT); extracellular vesicles
类别
资金
- European Union [667932, 223298]
- Science Foundation Ireland [SFI 09/SRC.B1794, SFI 12/RI/2338]
- H2020 Societal Challenges Programme [667932] Funding Source: H2020 Societal Challenges Programme
This study evaluated the anti-inflammatory and regenerative effects of bone marrow MSC and their extracellular vesicles in a diabetic fractured mouse model. The results showed that preconditioned cells promoted earlier soft callus formation and mineralization at the fracture site, suggesting the importance of preconditioning in MSC therapy research and optimization.
Background: Mesenchymal stem/stromal cells (MSC) have been employed successfully in immunotherapy and regenerative medicine, but their therapeutic potential is reduced considerably by the ischemic environment that exists after transplantation. The assumption that preconditioning MSC to promote quiescence may result in increased survival and regenerative potential upon transplantation is gaining popularity. Methods: The purpose of this work was to evaluate the anti-inflammatory and regenerative effects of human bone marrow MSC (hBM-MSC) and their extracellular vesicles (EVs) grown and isolated in a serum-free medium, as compared to starved hBM-MSC (preconditioned) in streptozotocin-induced diabetic fractured male C57BL/6J mice. Results: Blood samples taken four hours and five days after injection revealed that cells, whether starved or not, generated similar plasma levels of inflammatory-related cytokines but lower levels than animals treated with EVs. Nonetheless, starved cells prompted the highest production of IL-17, IL-6, IL-13, eotaxin and keratinocyte-derived chemokines and induced an earlier soft callus formation and mineralization of the fracture site compared to EVs and regularly fed cells five days after administration. Conclusions: Preconditioning may be crucial for refining and defining new criteria for future MSC therapies. Additionally, the elucidation of mechanisms underpinning an MSC's survival/adaptive processes may result in increased cell survival and enhanced therapeutic efficacy following transplantation.
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