Background—
Because mesenchymal stem cells (MSCs) induce proliferation and differentiation of c-kit+ cardiac stem cells (CSCs) in vivo and in vitro, we hypothesized that combining human (h) MSCs with c-kit+ hCSCs produces greater infarct size reduction compared with either cell administered alone after myocardial infarction (MI).
Methods and Results—
Yorkshire swine underwent balloon occlusion of the left anterior descending coronary artery followed by reperfusion and were immunosuppressed after MI with cyclosporine and methylprednisolone. Intramyocardial combination hCSCs/hMSCs (1 million cells/200 million cells, n=5), hCSCs alone (1 million cells, n=5), hMSCs alone (200 million cells, n=5), or placebo (phosphate-buffered saline; n=5) was injected into the infarct border zones at 14 days after MI. Phenotypic response to cell therapy was assessed by cardiac magnetic resonance imaging and micromanometer conductance catheterization hemodynamics. Although each cell therapy group had reduced MI size relative to placebo (P
Conclusions—
Combining hMSCs and hCSCs as a cell therapeutic enhances scar size reduction and restores diastolic and systolic function toward normal after MI. Taken together, these findings illustrate important biological interactions between c-kit+ CSCs and MSCs that enhance cell-based therapeutic responses.