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Natural killer cells impede the engraftment of cardiomyocytes derived from induced pluripotent stem cells in syngeneic mouse model.

Abstract：

: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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Nakamura Y,Miyagawa S,Yoshida S,Sasawatari S,Toyofuku T,Toda K,Sawa Y

doi

10.1038/s41598-019-47134-3

subject

Has Abstract

pub_date

2019-07-25 00:00:00

pages

10840

issue

1

issn

2045-2322

pii

10.1038/s41598-019-47134-3

journal_volume

9

pub_type

杂志文章

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