Natural killer cells impede the engraftment of cardiomyocytes derived from induced pluripotent stem cells in syngeneic mouse model
SCIENTIFIC REPORTS(2019)
摘要
Transplantation of cardiomyocytes derived from induced pluripotent stem cell (iPSC-CMs) is a promising approach for increasing functional CMs during end-stage heart failure. Although major histocompatibility complex (MHC) class I matching between donor cells and recipient could reduce acquired immune rejection, innate immune responses may have negative effects on transplanted iPSC-CMs. Here, we demonstrated that natural killer cells (NKCs) infiltrated in iPSC-CM transplants even in a syngeneic mouse model. The depletion of NKCs using an anti-NKC antibody rescued transplanted iPSC-CMs, suggesting that iPSC-CMs activated NKC-mediated innate immunity. Surprisingly, iPSC-CMs lost inhibitory MHCs but not activating ligands for NKCs. Re-expression of MHC class I induced by IFN-γ as well as suppression of activating ligands by an antibody rescued the transplanted iPSC-CMs. Thus, NKCs impede the engraftment of transplanted iPSC-CMs because of lost MHC class I, and our results provide a basis for an approach to improve iPSC-CM engraftment.
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关键词
Induced pluripotent stem cells,Innate immune cells,Science,Humanities and Social Sciences,multidisciplinary
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