Abstract
Background: Our previous studies demonstrated that adipose-derived mesenchymal stromal cells (ASCs) have immunomodulatory effects that prolong allograft survival in a rodent hind-limb allotransplant model. In this study, we investigated whether the effects of immunomodulation by ASCs on allograft survival are correlated with B cell regulation. Methods: B cells isolated from splenocytes were cocultured with ASCs harvested from adipose tissue from rodent groin areas for in vitro experiments. In an in vivo study, hind-limb allotransplantation from Brown-Norway to Lewis rats was performed, and rats were treated with ASCs combined with short-term treatment with anti-lymphocyte serum (ALS)/cyclosporine (CsA) as immunosuppressants. Peripheral blood and transplanted tissue were collected for further analysis. Result: An in vitro study revealed that ASCs significantly suppressed lipopolysaccharide-activated B cell proliferation and increased the percentage of Bregs. The levels of immunoregulatory cytokines, such as TGF-β1 and IL-10, were significantly increased in supernatants of stimulated B cells cocultured with ASCs. The in vivo study showed that treatment with ASCs combined with short-term ALS/CsA significantly reduced the B cell population in alloskin tissue, increased the proportion of circulating CD45Ra+/Foxp3+ B cells, and decreased C4d expression in alloskin. Conclusion: ASCs combined with short-term immunosuppressant treatment prolong allograft survival and are correlated with B cell regulation, C4d expression and the modulation of immunoregulatory cytokines.
Original language | English (US) |
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Article number | 478 |
Journal | Stem Cell Research and Therapy |
Volume | 11 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2020 |
Keywords
- Adipose-derived stromal cells
- Regulatory B cell
- Vascularized composite allotransplantation
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Molecular Medicine
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Cell Biology