Mesenchymal stromal cells to promote solid organ transplantation tolerance

Mesenchymal stromal cells (MSCs) possess unique immunomodulatory features. MSCs dampen effector T-cell response while promoting the emergence of regulatory T cells. By skewing this balance, MSC could represent the ideal strategy for tolerance induction in organ transplantation. Here we review recent evidence on the efficacy of MSC-based therapy in experimental models of solid organ transplantation as well as the early clinical experiences in kidney transplantation.

MSC infusion in experimental models of solid organ transplantation resulted in a Treg-mediated tolerance. MSC also synergized with low-dose or transient pharmacological immunosuppression in inducing long-term graft survival indicating that these cells could allow safe minimization of maintenance drug therapy. Early results from clinical studies in kidney transplant recipients reported encouraging results on the immunoregulatory effect of MSC, although posttransplant MSC infusion could associate with acute graft dysfunction (engraftment syndrome).

Immunoregulatory functions of MSC are not fixed but rather the result of microenvironment they encounter in vivo. Further studies are needed to establish how and wherein these cells have to be administered and how they may function to safely modulate host immune response in vivo in clinical transplant setting.