Abstract
BackgroundOur 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.MethodsB 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.ResultAn 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.ConclusionASCs combined with short-term immunosuppressant treatment prolong allograft survival and are correlated with B cell regulation, C4d expression and the modulation of immunoregulatory cytokines.
Highlights
Vascularized composite allotransplantation (VCA) has been used successfully in clinical applications in areas such as the face, upper limbs, larynx, penis, and uterus
adipose-derived mesenchymal stromal cells (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
ASCs suppressed B cell proliferation and increased the regulatory B cell population in vitro To investigate the immunomodulatory effects of ASCs on B cells, B cells were cocultured with ASCs in vitro
Summary
Vascularized composite allotransplantation (VCA) has been used successfully in clinical applications in areas such as the face, upper limbs, larynx, penis, and uterus. Our former study revealed that combined short-term anti-lymphocyte serum and cyclosporine A (ALS/CsA) treatment group could prolong allotransplant survival but still early rejection in a rodent hind-limb allotransplantation model [8]. Adipose-derived stromal cells (ASCs) combined short-term ALS/CsA could significantly increase the allotransplant survival as compared to that in ALS/ CsA alone group. Our previous studies demonstrated that ASCs combined with shortterm immunosuppressants (ALS/CsA) prolonged allograft survival through suppression of T cell proliferation and activation of regulatory T cell populations in a rodent/swine hind-limb VCA model [8,9,10]. 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. We investigated whether the effects of immunomodulation by ASCs on allograft survival are correlated with B cell regulation
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