Cellular cardiomyoplasty using embryonic cardiomyocytes and adult stem cells

Introduction: Terminal heart failure is independent to the underlying disease caused by a loss of functional cardiomyocytes. Currently in clinical trials and in animal experiments different cell types are used for cellular cardiomyoplasty. Methods: Experiments were performed in an autologous setting using transgenic mouse strains. Transgenic embryonic cardiomyocytes (n=98) and bone marrow cells (n=30) were injected into lesioned hearts of wild type mice. In control mice medium only was applied. Survival and further differentiation of transplanted cells was investigated by immunohistochemistry, alterations of myocardial function by left ventricular catheterization. Results: After transplantation of embryonic cardiomyocytes histology showed an elongated cell shape as well as cell contacts, suggesting differentiation, alignment and functional assembly. Immunohistochemistry demonstrated cross striation of transplanted cells. Furthermore left ventricular catheterization revealed significant improvement of left ventricular ejection fraction as well as cardiac output in treated compared to sham operated mice. Also transplanted transgenic bone marrow cells could be identified at different time points after injection. Immunohistochemistry showed no evidence for cardiac differentiation and functional investigation yielded no hemodynamic difference between treated and sham operated animals. Conclusions: Employing embryonic cardiomyocytes further differentiation of transplanted cells and a significant improvement of left ventricular function after cellular cardiomyoplasty could be shown. Intramyocardial injected bone marrow cells showed no evidence for cardiac differentiation and failed to improve left ventricular function.