Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium.
Transplantation of neonatal cardiomyocytes is a novel approach for the treatment of heart failure and myocardial infarction, but quantitative information on long-term cell survival and development is limited. Male donor cardiomyocytes were isolated from neonatal Fischer 344 rats (1-2 days), purified, and injected into the left ventricular wall of female syngeneic adult rats. One hour to 12 weeks later, genomic DNA was isolated from recipient hearts. The amount of male DNA per sample was determined by quantitative real-time TaqMan PCR of the male-specific Sry gene. Transplanted cell survival was 57 +/- 9% at 0-1 h, 24 +/- 6% at 24 h, 28 +/- 11% at 7 days, 27 +/- 3% at 14 days, 23 +/- 8% at 4 weeks and 15 +/- 3% at 12 weeks. The caspase inhibitor AcYVADcmk failed to improve transplanted cell survival at 24 h, suggesting that apoptosis did not play a major role in cell loss. Histology revealed that transplanted cells became more elongated over time, developed cross-striations, and that their nuclei increased in size. However, at 12 weeks, transplanted cells and their nuclei were still smaller than those of host myocardium. We established a quantitative survival profile for neonatal cardiomyocytes transplanted into normal adult myocardium. There was significant loss of cells within 24 h, but 15% of transplanted cells survived 12 weeks. Those cells that did survive underwent differentiation and developed visible sarcomeres, suggesting a potential contribution toward ventricular function.
Müller-Ehmsen
Jochen
J
Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Whittaker
Peter
P
Kloner
Robert A
RA
Dow
Joan S
JS
Sakoda
Tsuyoshi
T
Long
Tiffany I
TI
Laird
Peter W
PW
Kedes
Larry
L
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D002454:Cell Differentiation; D002470:Cell Survival / Q000502:physiology; D005260:Female; D006085:Graft Survival; D006321:Heart / Q000502:physiology*; D016027:Heart Transplantation; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000502:physiology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology; D014184:Transplantation, Homologous