Contribution of human adipose tissue-derived stem cells and the secretome to the skin allograft survival in mice.

Background: Despite considerable evidence showing the immunosuppressive properties of mesenchymal stem cells (MSCs) in vitro, such properties have not been fully demonstrated in vivo. The aim of this study was to evaluate the effect of MSCs and/or MSC secretome in inducing tolerance in a mouse skin transplantation model.

Methods: After receiving full-thickness skin allotransplantation on the back of the mouse, the recipient mice were infused with phosphate-buffered saline, adipose tissue-derived stem cells (ASCs), conditioned media (CM), and control media. Specifically, ASCs (1.0 × 10(6)/0.1 mL) were transplanted to ASC-infused mice and 25-fold concentrated CM, which had been obtained from ASC culture were infused to CM-infused mice. Graft survival rates and the parameters reflecting immunologic consequences were assessed.

Results: The serum level of proinflammatory cytokine interleukin 6 decreased in mice treated with ASCs or CM compared with the control groups after infusion (P < 0.05). Interferon gamma, interleukin 10, and tumor necrosis factor alpha messenger RNA levels in the skin graft seemed to be decreased in the ASC-infused mice and CM-infused mice. Hyporesponsiveness was identified in mixed lymphocyte reaction assay at 30-d posttransplantation in ASC- or CM-infused mice. And, administering ASCs and CM markedly increased skin allograft survival compared with control animals (P < 0.001).

Conclusions: These findings suggest that ASCs and their secretome have the potential to induce immunologic tolerance. Moreover, our results demonstrate that the immunosuppressive properties of ASCs are mediated by the ASC secretome. Our approach could provide insights into a promising strategy to avoid toxicities of chemical immunosuppressive regimen in solid organ transplantation.