Cell-Based Therapies for Cardiac and Vascular Regeneration in Cardiovascular Disease: Recent Advances, Translational Barriers, and Future Directions

Abstract

Simple Summary Cardiovascular diseases are the leading cause of death worldwide, accounting for 19.2 million deaths in 2023. When a heart attack occurs, the affected cardiomyocytes die rapidly, and the adult heart replaces them at only about 1% per year, far too slowly to compensate for the loss following a large infarction. Current treatments stabilise patients but cannot rebuild lost muscle. Over the past two decades, clinical trials have tested stem cells from bone marrow, fat tissue, umbilical cord blood, and reprogrammed adult cells. These approaches are consistently safe. Some have produced modest improvements in cardiac function and scar reduction, but the transplanted cells rarely persist long enough to form new heart muscle. The benefit they confer appears to arise mainly from signalling particles they release called extracellular vesicles and exosomes, which carry microRNAs and proteins that reduce scarring, stimulate blood vessel growth, and dampen post-injury inflammation. This finding has opened a new research direction: engineering those particles directly, without transplanting cells at all. This review examines the full range of cell-based strategies studied to date, the clinical trial evidence, the barriers to progress, and what engineered vesicles, bioengineered tissue constructs, gene editing, and improved trial design might offer.