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


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 alpha-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.
Naito
H
H
Department of Surgery III, Nara Medical University, Nara, Japan. naitoh@naramed-u.ac.jp
Nishizaki
K
K
Yoshikawa
M
M
Yamada
T
T
Satoh
H
H
Nagasaka
S
S
Kiji
T
T
Taniguchi
S
S
D000200:Action Potentials; D002454:Cell Differentiation; D002455:Cell Division; D006321:Heart / Q000196:embryology*; D016027:Heart Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D032342:Muscle Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous