Vasculogenically conditioned peripheral blood mononuclear cells inhibit mouse immune response to induced pluripotent stem cell-derived allogeneic cardiac grafts.

Abstract

Allogeneic transplantation of induced pluripotent stem cell (iPSC)-derived cardiomyocytes is apromising treatment for cardiac diseases, although immune rejection by the recipient poses a concern. In this study, we aimed to investigate whether concomitant transplantation of vasculogenically conditioned peripheral blood mononuclear cells, which are otherwise immunosuppressive, may enhance graft survival. Luciferase-transduced, iPSC-derived cardiomyocytes from C57BL/6 mice were transplanted to the dorsal subcutaneous space of syngeneic C57BL/6 mice (n = 19), allogeneic Balb/c mice treated with (n = 20) or without (n = 20) immunosuppressants, and those injected with vasculogenically conditioned peripheral blood mononuclear cells (n = 20). Although graft survival, assessed by bioluminescence, was comparable among the groups initially, it improved significantly at days 7 and 10 in allogeneic transplanted mice treated with vasculogenically conditioned peripheral blood mononuclear cells than in others (P < 0.01). Our results proved that cell-based immunosuppression may boost clinical outcomes from allogeneic cell therapy.