Sca1+ mesenchymal stromal cells inhibit graft-versus-host disease in mice after bone marrow transplantation

• Sca1+ MSCs subset can ameliorate and attenuate the progress of GVHD, and prolong the survival of mice with allogeneic HCT.
• Sca1+ MSCs suppress GVHD by reducing T lymphocyte infiltration and inhibiting CD80/CD86 expression on splenic DCs.
• The suppression of co-stimulatory molecules on splenic DCs may be mediated via upregulation of CTLA-4 expression.

Mesenchymal stromal cells (MSCs) have therapeutic potential for the prevention and treatment of graft-versus-host disease (GVHD). However, MSCs comprise several subpopulations, which have not been individually assessed for their role in GVHD suppression. In this study, we assessed the immunosuppressive effect of bone-related Sca1+ MSCs on acute GVHD in a MHC-mismatched mouse model of allogeneic hematopoietic stem cell transplantation (HCT). Our results showed that Sca1+ MSCs decreased the severity of acute GVHD (aGVHD) and prolonged the survival period of allogeneic HCT recipients. This effect was exerted through lowered T lymphocyte infiltration in target organs and by inhibition of CD80/86 expression on host dendritic cells. Furthermore, the expression of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of T cells, was elevated in the recipient splenocytes. In conclusion, bone-related Sca1+ MSCs subpopulation suppressed GVHD and could be a novel treatment for acute GVHD.