%0 Journal Article
%T Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques.
%A Lin Y
%A Sato N
%A Hong S
%A Nakamura K
%A Ferrante EA
%A Yu ZX
%A Chen MY
%A Nakamura DS
%A Yang X
%A Clevenger RR
%A Hunt TJ
%A Taylor JL
%A Jeffries KR
%A Keeran KJ
%A Neidig LE
%A Mehta A
%A Schwartzbeck R
%A Yu SJ
%A Kelly C
%A Navarengom K
%A Takeda K
%A Adler SS
%A Choyke PL
%A Zou J
%A Murry CE
%A Boehm M
%A Dunbar CE
%J Cell Stem Cell
%V 31
%N 7
%D 2024 Jul 5
%M 38843830
%F 25.269
%R 10.1016/j.stem.2024.05.005
%X Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.