Differential response of human cardiac stem cells and bone marrow mesenchymal stem cells to hypoxia-reoxygenation injury.

Cardiosphere-derived cells (CDCs) and bone marrow mesenchymal stem cells (MSCs) are popularly used in stem cell therapy for myocardial regeneration. The cell type that survives and maintains stem cell characteristics in the adverse microenvironment following ischemia-reperfusion injury is presumed to be ideal for transplantation. The study was therefore aimed at identifying the cell type with relatively greater resistance to ischemia-reperfusion injury. CDCs were isolated from the right atrial appendage and MSCs from bone marrow of patients who underwent coronary artery bypass graft surgery. Ischemia-reperfusion injury was simulated in vitro by subjecting the cells to hypoxia (0.5% O2) followed by reintroduction of oxygen (HR injury). Greater resistance of CDCs to HR injury was apparent from the decreased expression of senescence markers and lower proportion of apoptotic cells (one-sixth of that in MSCs). HR injury retarded cell cycle progression in MSCs. Consequent to HR injury, cell migration and secretion of stromal-derived growth factor were stimulated, significantly in CDCs. The differentiation to myocyte lineage and angiogenesis assessed by tube formation ability was better for CDCs. Release of vascular endothelial growth factor was relatively more in CDCs and was further stimulated by HR injury. Differentiation to osteogenic and angiogenic lineage was stimulated by HR injury in MSCs. Compared to MSCs, CDCs appear to be the cell of choice for promoting myocardial regeneration by virtue of its survival capacity in the event of ischemic insult along with higher proliferation rate, migration efficiency, release of growth factors with paracrine effects and differentiation to cardiac lineage.