on March 25, 2002
Published online before print March 25, 2002, doi: 10.1161/01.CIR.0000013782.76324.92
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Submitted on December 3, 2001
From the Heart Institute (J.M.-E., P.W., J.S.D., R.A.K.), Good Samaritan Hospital, Los Angeles, Calif; the Institute for Genetic Medicine (J.M.-E., L.K.), the Department of Medicine (P.W., R.A.K.), Norris Cancer Center (T.I.L., P.W.L.), Keck School of Medicine, University of Southern California, Los Angeles; the Department of Internal Medicine III (J.M.-E.), University of Cologne, Germany; and the Division of Cardiology (K.L.P.), Department of Medicine, University of California, San Diego. * To whom correspondence should be addressed. E-mail: rkloner{at}goodsam.org.
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. Methods and Results—Cardiomyocytes from male neonatal Fischer 344 rats (1 to 2 days, 3 to 5x106) 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 µm, 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.
Revised on January 30, 2002
Accepted on January 30, 2002
Rebuilding a Damaged Heart. Long-Term Survival of Transplanted Neonatal
Rat Cardiomyocytes After Myocardial Infarction and Effect on Cardiac
Function
Jochen Müller-Ehmsen MD,
Key words: ventricles • cells • transplantation • angiography • myocardial infarction
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