Mesenchymal Stem Cells and Their Exosomes in Cardiac Repair: Advances and Future Directions

Cardiovascular disease remains the leading global cause of death, with rising prevalence and mortality, underscoring the need for regenerative strategies. This review synthesizes evidence on mesenchymal stromal/stem cells and their exosomes in cardiac repair. Preclinical studies show paracrine-driven benefits such as pro-angiogenic, anti-apoptotic, anti-fibrotic, and immunomodulatory effects, which may be driven in part by exosomal cargo such as microRNAs. Early clinical trials establish safety and signal improvements in remodeling and function, however, Phase III trial results have been mixed, and no MSC-based product has yet been approved for routine clinical use. We also discuss next-generation induced pluripotent stem cells-derived mesenchymal stromal/stem cells, which offer scalability and consistency but require rigorous control of residual pluripotency and tumorigenicity risk. Future priorities include standardized GMP manufacturing, source and payload optimization, targeted delivery (including cell-free exosomes and biomaterials), and biomarker-guided patient selection to enable effective clinical translation.