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

血管生成条件性外周血单核细胞抑制小鼠对诱导性多能干细胞衍生的同种异体心脏移植物的免疫反应

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作者:Noriyuki Kashiyama, Shigeru Miyagawa, Satsuki Fukushima, Takuji Kawamura, Ai Kawamura, Shohei Yoshida, Yuki Nakamura, Akima Harada, Haruchika Masuda, Koichi Toda, Takayuki Asahara, Yoshiki Sawa

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.

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