Adipose tissue-derived mesenchymal stem cells increase skin allograft survival and inhibit Th-17 immune response

Adipose tissue-derived mesenchymal stem cells (ADSC) exhibit immunosuppressive capabilities both in vitro and in vivo. Their use for therapy in the transplant field is attractive as they could render the use of immunosuppressive drugs unnecessary. The aim of this study was to investigate the effect of ADSC therapy on prolonging skin allograft survival. Animals that were treated with a single injection of donor allogeneic ADSC one day after transplantation showed an increase in donor skin graft survival by approximately one week. This improvement was associated with preserved histological morphology, an expansion of CD4(+) regulatory T cells (Treg) in draining lymph nodes, as well as heightened IL-10 expression and down-regulated IL-17 expression. In vitro, ADSC inhibit naïve CD4(+) T cell proliferation and constrain Th-1 and Th-17 polarization. In summary, infusion of ADSC one day post-transplantation dramatically increases skin allograft survival by inhibiting the Th-17 pathogenic immune response and enhancing the protective Treg immune response. Finally, these data suggest that ADSC therapy will open new opportunities for promoting drug-free allograft survival in clinical transplantation.

State of Sao Paulo Foundation for Research Support (FAPESP), 07/07139-3

State of Sao Paulo Foundation for Research Support (FAPESP), 06/55326-4

State of Sao Paulo Foundation for Research Support (FAPESP), 10/52180-4

State of Sao Paulo Foundation for Research Support (FAPESP), 12/02270-2

Brazilian Council of Scientific and Technologic Development (470533/2007-2, CNPq/DECIT/MS)

Coordination of Improvement of Higher Education Personnel (CAPES Bex-2236/09-5)