Pericardial Delivery of Stem Cells: An Emerging Frontier in Myocardial Regeneration for Ischemic Heart Disease

Cardiac regenerative therapies have seen limited clinical translation due to persistent challenges in stem cell viability, retention, and demonstration of efficacy. The pericardial space, however, has emerged as a dynamic reservoir of bioactive substances capable of modulating cellular processes within the myocardium. Pericardial delivery of stem cells offers a promising solution to modern translational roadblocks by leveraging the pericardial space for its proximity to the heart, protective compartmentalization, and favorable biochemical milieu. Preclinical studies using cardiospheres, cardiosphere-derived cells, and mesenchymal stem cells have demonstrated significant improvements in cardiac function, infarct size reduction, and vascular regeneration after myocardial infarction. Additionally, epicardial hydrogels and percutaneous pericardial injections have been shown to reduce local immune responses and enable broader therapeutic distribution compared with intramyocardial and intracoronary approaches. As a potential cardiac surgical adjuvant therapy, pericardial delivery of stem cells represents an exciting frontier in cardiac regeneration, warranting further research to define its role in clinical practice.