The immunosuppressive properties of non-cultured dermal-derived mesenchymal stromal cells and the control of graft-versus-host disease

Mesenchymal stromal cells (MSCs) have been developed for the prevention and treatment of graft-versus-host disease (GVHD). Non-cultured natural MSCs are considered ideal, as they better maintain their biological and therapeutic properties. The skin is the largest organ in the body and constitutes an interesting alternative to bone marrow for the generation of MSCs. Large numbers of dermal-derived-MSCs (DMSCs) can be easily generated without culturing in vitro, but their therapeutic effects still remain unclear. In this study, we described for the first time the use of non-cultured DMSCs for controlling GVHD in an MHC-mismatched mouse model and investigated their immunomodulatory effects. Our results showed that non-cultured mouse DMSCs decreased the incidence and severity of acute GVHD during MHC-mismatched stem cell transplantation in mice. This effect was mediated by the inhibition of splenic cell (SPC) proliferation and the enhancement of Treg cells. Consistent with the results in vivo, the results in vitro showed that human DMSCs inhibited the proliferation of peripheral blood mononuclear cells (PBMCs) by inhibiting the proliferation of CD3+ T cells. hDMSCs prevented PBMCs from entering S phase, suppressed the activation of CD3+ T cells and increased Treg proportions. In conclusion, DMSCs should be considered as a novel MSC source for the control of refractory GVHD.