Xenogeneic embryonic stem cell–derived cardiomyocyte transplantation

Abstract 

Purpose

The purpose of this study was to investigate the survival of xenogeneic embryonic stem cell (ES cell)–derived cardiomyocytes transplanted into the normal myocardium.

Material and methods

Undifferentiated mouse ES cells carrying the enhanced green fluorescent protein (EGFP) were cultured in hanging drops and then plated onto dishes. These cells were identified as cardiomyocytes by the expression of cardiac-specific genes, recording of action potential, and immunostaining with anti-sarcomeric myosin antibody. Donor cells were injected into the normal myocardium, with cyclosporine administered daily. One week after the transplantation, we investigated donor cell survival by examining EGFP expression, hematoxylin and eosin staining, and immunostaining with anti-sarcomeric myosin antibody.

Results

In vitro donor cells derived from ES cells expressed myosin light chain-2v and α-myosin heavy chain genes, had action potentials of a ventricular myocyte type, and were stained by anti-sarcomeric myosin antibody. In vivo 1 week after transplantation, EGFP-expressed cells were detected in the cell transplanted area. No lymphocytic infiltration was observed around these cells.

Conclusions

ES cell–derived cardiomyocytes survived in the normal myocardium after the transplantation, even in a discordant xenogeneic transplantation model. These results indicate that cell transplantation using cardiomyocytes derived from ES cells, even if xenogeneic represents an attractive strategy for treating heart disease.