{Reference Type}: Journal Article
{Title}: Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques.
{Author}: Lin Y;Sato N;Hong S;Nakamura K;Ferrante EA;Yu ZX;Chen MY;Nakamura DS;Yang X;Clevenger RR;Hunt TJ;Taylor JL;Jeffries KR;Keeran KJ;Neidig LE;Mehta A;Schwartzbeck R;Yu SJ;Kelly C;Navarengom K;Takeda K;Adler SS;Choyke PL;Zou J;Murry CE;Boehm M;Dunbar CE;
{Journal}: Cell Stem Cell
{Volume}: 31
{Issue}: 7
{Year}: 2024 Jul 5
{Factor}: 25.269
{DOI}: 10.1016/j.stem.2024.05.005
{Abstract}: 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.