Dual stem cell therapy synergistically improves cardiac function and vascular regeneration following myocardial infarction

TLDR

Both myocardium and vasculature are severely damaged after myocardial infarction, so therapies must target both to achieve true cardiac repair. The study demonstrates a dual therapy using hiPSC‑derived cardiomyocytes and hMSC‑loaded patches to enhance cardiac repair in a rat MI model. Epicardial hMSC patches create a paracrine‑rich microenvironment that boosts vascular regeneration and markedly improves retention and engraftment of injected hiPSC‑CMs, restoring cardiac function. Injected hiPSC‑CMs adopt adult‑like morphology, and the dual therapy shows compelling evidence of enhanced cardiac repair in MI hearts.

Abstract

Abstract Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to achieve true cardiac repair. Here we demonstrate a concomitant method that exploits the advantages of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cell-loaded patch (hMSC-PA) to amplify cardiac repair in a rat MI model. Epicardially implanted hMSC-PA provide a complimentary microenvironment which enhances vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improves the retention and engraftment of intramyocardially injected hiPSC-CMs which ultimately restore the cardiac function. Notably, the majority of injected hiPSC-CMs display adult CMs like morphology suggesting that the secretomic milieu of hMSC-PA constitutes pleiotropic effects in vivo. We provide compelling evidence that this dual approach can be a promising means to enhance cardiac repair on MI hearts.