Abstract: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have gained significant attention in the treatment of ischemic heart disease. However, challenges such as immune rejection and low retention rates still hinder their therapeutic potential. Human adipose-derived mesenchymal stromal cells (hADSCs) have been shown to modulate immune responses, promote angiogenesis, and improve the maturation of hiPSC-CMs. In this study, we co-cultured hiPSC-CMs and hADSCs on a biodegradable poly (D, L-lactic-co-glycolic acid) (PLGA) fiber scaffold for several days to generate a composite 231.00 ± 15.14 μm thick 3D cardiac tissue sheet. As anticipated, the resulting tissue exhibited improved structure, alignment, extracellular matrix (ECM) condition, contractility, and paracrine activity compared to hiPSC-CMs cultured alone on the PLGA fibers. Additionally, the composite tissue sheet significantly enhanced cell engraftment and survival following transplantation. In a rat myocardial infarction model, this composite tissue not only improved cardiac function but also reduced ventricular remodeling, fibrosis, and promoted angiogenesis. These findings suggest that this composite 3D cardiac tissue sheet could represent a promising therapeutic approach for clinical applications.
