Stem cell-based therapy in cardiac repair after myocardial infarction: Promise, challenges, and future directions.

Stem cells represent an attractive resource for cardiac regeneration. However, the survival and function of transplanted stem cells is poor and remains a major challenge for the development of effective therapies. As two main cell types currently under investigation in heart repair, mesenchymal stromal cells (MSCs) indirectly support endogenous regenerative capacities after transplantation, while induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) functionally integrate into the damaged myocardium and directly contribute to the restoration of its pump function. These two cell types are exposed to a common microenvironment with many stressors in ischemic heart tissue. This review summarizes the research progress on the mechanisms and challenges of MSCs and iPSC-CMs in post-MI heart repair, introduces several randomized clinical trials with 3D-mapping-guided cell therapy, and outlines recent findings related to the factors that affect the survival and function of stem cells. We also discuss the future directions for optimization such as biomaterial utilization, cell combinations, and intravenous injection of engineered nucleus-free MSCs. • IPSC-CMs and MSCs have emerged as the most promising options for ischemic myocardial repair. • The survival and function of transplanted stem cells is poor and remains a major challenge for the development of effective therapies. • Three stress conditions affect the survival and function of stem cells in the ischemic heart: low oxygen/nutrients, metabolic disorders, and inflammation. • Future studies may focus on the selection of patients, the optimization of stem cells, the combination of cells with biomaterials, and repeated intravenous delivery. [ABSTRACT FROM AUTHOR]