Abstract
Cardiovascular diseases remain the leading cause of mortality worldwide and continue to impose a substantial clinical burden despite major advances in pharmacological and interventional therapies. Because the adult myocardium has limited regenerative capacity, irreversible cardiomyocyte loss frequently leads to adverse remodeling and progressive heart failure (HF). Mesenchymal stromal cells (MSCs) are among the most extensively studied cell therapies for cardiac repair because of their immunomodulatory, pro-angiogenic, anti-inflammatory, and anti-fibrotic effects, mediated predominantly through paracrine signaling. This review summarizes the current evidence for MSC-based therapy in ischemic heart disease (IHD), coronary and microvascular disorders, myocardial infarction, HF, myocarditis, pulmonary arterial hypertension, and valvular heart disease (VHD). We discuss MSC sources, preclinical and clinical evidence, manufacturing and dosing, delivery routes, biomaterial-assisted transplantation, preconditioning, genetic modification, and imaging for cell tracking and treatment monitoring. Although MSC therapy has shown a favorable safety profile and regenerative potential, clinical efficacy remains variable because of limited cell survival, poor myocardial retention, and heterogeneous treatment protocols. Further optimization of manufacturing, delivery, and patient selection, together with well-designed randomized trials, is required to establish standardized protocols and support clinical translation.