Rebuilding a damaged heart: long-term survival of transplanted neonatal rat cardiomyocytes after myocardial infarction and effect on cardiac function.
BACKGROUND
The long-term effects of cardiac cell transplantation on cardiac function are unknown. Therefore, we tested the survival and functional impact of rat neonatal cardiac myocytes up to 6 months after transplantation into infarcted hearts.


RESULTS
Cardiomyocytes from male neonatal Fischer 344 rats (1 to 2 days, 3 to 5x10(6)) or medium was injected into the infarcts of adult syngeneic female animals 1 week after left coronary artery ligation. Six months later, implanted cardiomyocytes were still present by quantitative TaqMan polymerase chain reaction and histology. In all treated hearts, discrete lumps of cells were present within the infarct scar, which was not observed in media-injected hearts typified by a transmural infarct scar. Infarct thickness was greater in treated animals versus control animals (909+/-97 versus 619+/-43 microm, P<0.02), whereas infarct size and left ventricular volumes were similar. By biplane angiography, left ventricular ejection fractions at 6 months were greater (0.36+/-0.03 versus 0.25+/-0.02, P<0.01) and significantly less infarct zone dyskinesis was seen (0.30+/-0.08 versus 0.55+/-0.07, P=0.035, lateral projection) in treated animals versus control animals.


CONCLUSIONS
Grafted neonatal cardiomyocytes were present in infarcts 6 months after transplantation; they thickened the wall of the left ventricle and were associated with enhanced ejection fraction and reduced paradoxical systolic bulging of the infarct. Therefore, neonatal cardiac cell transplants exhibit long-term survival in a myocardial infarct model and contribute to long-term improved cardiac function. These results suggest that a damaged heart can be rebuilt.
Müller-Ehmsen
Jochen
J
Heart Institute, Good Samaritan Hospital, Los Angeles, Calif 90017, USA.
Peterson
Kirk L
KL
Kedes
Larry
L
Whittaker
Peter
P
Dow
Joan S
JS
Long
Tiffany I
TI
Laird
Peter W
PW
Kloner
Robert A
RA
D000818:Animals; D000831:Animals, Newborn; D002469:Cell Separation; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D017023:Coronary Angiography; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival; D006352:Heart Ventricles / Q000166:cytology / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000166:cytology*; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D013995:Time; D016896:Treatment Outcome; D016277:Ventricular Function, Left