Abstract 259: Role of Connexin 43 in Human Bone Marrow Derived Mesenchymal Stem Cell Cardiac Integration and Cardiac Stem cell Niche Formation.

Introduction: Bone marrow-derived mesenchymal stem cells (MSCs) and cardiac progenitor cells (CPCs) have been used successfully as a cell-based approach for cardiac regeneration after myocardial infarction. While MSCs and CPCs are effective, in part due to differentiation, paracrine effect, and integration into the heart, the mechanism underlying these effects remains controversial. Objective: We hypothesized that functional connexin 43 (Cx43) gap junctions are crucial for MSC and CPCs interaction and integration into cardiac tissue and cardiac stem cell niche formation. Methods and Results: Human MSCs were co-cultured with neonatal rat ventricular cardiomyocytes (NRVMs). The ability of MSCs to form gap junctions was modulated using lentiviral constructs to either knockdown (Cx43KD) or overexpress (Cx43OE) Cx43. Co-culture of Cx43OE or control MSCs with NRVMs led to the formation of beating, three-dimensional tubes whereas Cx43KD MSCs failed to form tubes (n=5, p Conclusion: These findings reveal that cell−cell contact mediated by Cx43 gap junctions enables MSCs to interact with CPCs, integrate and reconstitute cardiac stem cell niches.