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Background  Infusion of allogeneic cardiosphere‐derived cells (allo‐ CDC s) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long‐term effects of allo‐ CDC s have not been assessed. We performed a placebo‐controlled pivotal study for long‐term evaluation, as well as shorter‐term mechanistic studies.    Methods and Results  Minipigs underwent 1.5‐hour mid‐left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo‐ CDC s or vehicle 30 minutes postreperfusion. Left ventriculography ( LVG ) demonstrated preserved ejection fraction ( EF ) and attenuation of  LV  remodeling in  CDC ‐treated pigs. Pigs underwent cardiac magnetic resonance imaging ( MRI ) and  LVG  1 hour and 8 weeks after therapy to evaluate efficacy.  MRI  showed improvement of  EF  and attenuation of  LV  remodeling immediately after allo‐ CDC  infusion. In addition, allo‐ CDC s improved regional function and decreased hypertrophy 2 months post‐treatment. Histological analysis revealed increased myocardial salvage index, enhanced vascularity, sustained reductions in infarct size/area at risk and scar transmurality, and attenuation of collagen deposition in the infarct zone of allo‐ CDC ‐treated pigs at 2 months. Allo‐ CDC s did not evoke lymphohistiocytic infiltration or systemic humoral memory response. Short‐term experiments designed to probe mechanism revealed antiapoptotic effects of allo‐ CDC s on cardiomyocytes and increases in cytoprotective macrophages, but no increase in overall inflammatory cell infiltration 2 hours after cell therapy.    Conclusions  Allo‐ CDC  infusion postreperfusion is safe, improves cardiac function, and attenuates scar size and remodeling. The favorable effects persist for at least 2 months after therapy. Thus, cellular postconditioning confers not only acute cardioprotection, but also lasting structural and functional benefits.

journal of the american heart association

Durable Benefits of Cellular Postconditioning: Long‐Term Effects of Allogeneic Cardiosphere‐Derived Cells Infused After Reperfusion in Pigs with Acute Myocardial Infarction