Regenerative Stem Cell Therapy for Cardiac Repair

Abstract

Myocardial infarction (MI) causes irreversible loss of cardiomyocytes, replaced by non-contractile fibrotic scar tissue that progressively impairs cardiac function and leads to heart failure. Stem cell-based cardiac regeneration aims to restore functional myocardium through cell replacement, paracrine signalling, and neovascularisation. This study compared four stem cell delivery strategies for post-MI cardiac repair in a rat permanent left anterior descending (LAD) ligation model (n = 12/group): (i) intramyocardial injection of human iPSC-derived cardiomyocytes (iPSC-CMs); (ii) iPSC-CM-seeded decellularised extracellular matrix (dECM) cardiac patches; (iii) cardiac progenitor cell (CPC)-derived exosomes; and (iv) a combined patch + exosome strategy. At 4 weeks post-treatment, dECM patches seeded with iPSC-CMs achieved the greatest improvement in left ventricular ejection fraction (LVEF: +14.8 +- 2.4% above MI-only control; p < 0.001), significantly exceeding intramyocardial injection (+8.4 +- 2.2%; p = 0.002) and exosomes alone (+6.2 +- 1.8%; p < 0.001). The combined patch + exosome group achieved the highest absolute LVEF recovery (+16.4 +- 2.8%; p < 0.001) with 2.4-fold higher capillary density and 42% smaller infarct size versus MI-only controls. Engrafted iPSC-CMs in patches showed evidence of electromechanical coupling (connexin-43 expression at graft-host border) and synchronised calcium transients by optical mapping. These results establish the combined dECM patch + exosome strategy as the most efficacious stem cell approach for post-MI cardiac repair.