BACKGROUND: Cardiovascular diseases remain the leading cause of mortality, accounting for almost 18 million deaths yearly, with CAD/ACS responsible for most disease burden. Conventional treatment reduces inflammation, fibrosis, scar tissue formation, and cardiac remodeling but does not address cardiomyocyte loss.

OBJECTIVE: Review stem cells evaluated for cardiomyocyte regeneration, routes of administration, structural and functional outcomes, complications, and ethical limitations from preclinical and clinical studies, and recommend an ideal choice.

METHODOLOGY: Sixty-eight articles were selected from original and review articles on PubMed, Google Scholar, Web of Science, and NIH. Data were obtained from AHA, CDC, WHO, ISHLT, and clinicaltrials.gov.

DISCUSSION: ACS results in cardiomyocyte loss, inflammation, repair by fibrosis, scar tissue formation, cardiac remodeling, and reduced cardiac function, progressing to heart failure. While conventional treatment addresses most outcomes, it does not address cardiomyocyte loss. For few patients who benefit from heart transplants, rejection, infection, vasculopathy, and malignant transformation reduce the 3-year allograft survival rate to 75% and 4% annual death rate thereafter. Stem cell therapy promises to promote regeneration, improve cardiac function, and halt progression to heart failure. While improved structural and functional outcomes were observed with different stem cells studied, the administration route, stem cell retention, complications, and ethical limitations need to be considered in selecting an ideal choice.

CONCLUSION: Stem cell therapy for CAD/ACS is a promising therapeutic approach to improve cardiac function, halt progression to HF and decrease disease burden. Evidence points to administration via cellular scaffolds for optimal cell retention. In selecting an ideal choice, long-term studies are needed to evaluate complications and how to mitigate them to improve prognosis.