Cardiovascular diseases remain the leading cause of global morbidity and mortality, with the limited intrinsic regenerative capacity of the adult heart contributing to poor outcomes. Stem cell therapy represents a promising strategy to restore myocardial function; however, the evidence base is fragmented, with limited comprehensive synthesis on the applications of stem cells in human cardiovascular regeneration. This review aimed to assess current evidence on stem cell applications for cardiovascular repair and regeneration. A search of PubMed, Web of Science, and the Cochrane Library was performed, supplemented by Google Scholar, to identify clinical studies published between January 1, 2020 and December 31, 2025. Data extraction focused on study design, patient demographics, interventions, delivery methods, and outcomes. Findings were synthesized narratively. A total of 27 clinical studies, reporting findings on diverse stem cell populations, were included. Stem cells used in cardiac regenerative therapy include mesenchymal stromal cells, bone marrow-derived mesenchymal stromal cells, mesenchymal precursor cells, adipose-derived stem cells, stem/progenitor cells, umbilical cord blood-derived mononuclear cells, cardiosphere-derived cells, cardiopoietic stem cells, human-induced pluripotent stem cell-derived cardiomyocytes, and multilineage-differentiating stress-enduring cells. Findings demonstrate that stem cell therapies are safe and feasible, with improvements observed in surrogate endpoints. However, long‑term follow‑up often reveals attenuation of early benefits. Advancements in therapy include delivery methods, with hydrogel encapsulation, engineered grafts, and patch‑based implantation showing promise in enhancing cell survival and retention. Paracrine‑focused approaches, including extracellular vesicle-enhanced therapy and secretome administration, show promising advancements, and novel cell types such as Muse cells, mesenchymal progenitor cells, and cardiosphere-derived cells represent frontiers in regenerative cardiology. Current evidence supports the promise of stem cells for cardiovascular repair and regeneration, though robust long-term clinical outcomes remain to be established.
Sanyaolu et al. (2026) studied this question.