TY - JOUR
T1 - Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction
AU - Etzion, Sharon
AU - Battler, Alexander
AU - Barbash, Israel M.
AU - Cagnano, Emanuela
AU - Zarin, Parvin
AU - Granot, Yosef
AU - Kedes, Laurence H.
AU - Kloner, Robert A.
AU - Leor, Jonathan
N1 - Funding Information:
We wish to thank Mrs Maya Rovner for technical assistance in the echocardiography studies. This work was supported by grant No. 95-00294/1 and 98-414 from the United States-Israel Binational Science Foundation grant No. 3619 from the Israel Ministry of Health Sciences. Dr Kloner is supported by a grant from the National Heart, Lung and Blood Institute HL 61488. Dr Kedes is supported by a grant from the National Heart, Lung and Blood Institute.
PY - 2001/1/1
Y1 - 2001/1/1
N2 - Cell transplantation has been proposed as a future therapy for various myocardial diseases. It is unknown, however, whether the encouraging results obtained in animal models of ischemia and reperfusion, cryoinjury or cardiomyopathy can be reproduced in the setting of permanent coronary artery occlusion and extensive myocardial infarction (MI). Embryonic cardiac cells were isolated and cultured for 3 days to confirm viability, morphology and to label cells with BrdU or the reporter gene LacZ. Seven days after extensive MI, rats were randomized to cell (1.5 x 106) transplantation (n = 11) or culture medium injection (n = 16) into the myocardial scar. Echocardiography study was performed before and 53 ± 3 days after implantation to assess left ventricular (LV) remodeling and function. During follow-up, there was no mortality among cell-treated rats v 4 of 16 control rats (P = 0.12), X-gal staining, BrdU and α-SMA immunohistochemistry identified the engrafted cells 1 week, 4 weeks and 8 weeks after transplantation, respectively. Antibodies against α-SMA, connexin-43, fast and slow myosin heavy chain revealed grafts in various stages of differentiation in 10 of 11 cell-treated hearts. Many of them, however, kept their embryonic phenotype and were isolated from the host myocardium by scar tissue. Serial echocardiography studies revealed that cell transplantation prevented scar thinning. LV dilatation and dysfunction while control animals developed scar thinning, significant LV dilatation accompanied by progressive deterioration in LV contractility. Transplantation of embryonic cardiomyocytes after extensive MI in a rat model attenuate LV dilatation, infarct thinning, and myocardial dysfunction. Still, many grafts remain isolated and do not differentiate into an adult phenotype, even when studied 2 months alfer grafting.
AB - Cell transplantation has been proposed as a future therapy for various myocardial diseases. It is unknown, however, whether the encouraging results obtained in animal models of ischemia and reperfusion, cryoinjury or cardiomyopathy can be reproduced in the setting of permanent coronary artery occlusion and extensive myocardial infarction (MI). Embryonic cardiac cells were isolated and cultured for 3 days to confirm viability, morphology and to label cells with BrdU or the reporter gene LacZ. Seven days after extensive MI, rats were randomized to cell (1.5 x 106) transplantation (n = 11) or culture medium injection (n = 16) into the myocardial scar. Echocardiography study was performed before and 53 ± 3 days after implantation to assess left ventricular (LV) remodeling and function. During follow-up, there was no mortality among cell-treated rats v 4 of 16 control rats (P = 0.12), X-gal staining, BrdU and α-SMA immunohistochemistry identified the engrafted cells 1 week, 4 weeks and 8 weeks after transplantation, respectively. Antibodies against α-SMA, connexin-43, fast and slow myosin heavy chain revealed grafts in various stages of differentiation in 10 of 11 cell-treated hearts. Many of them, however, kept their embryonic phenotype and were isolated from the host myocardium by scar tissue. Serial echocardiography studies revealed that cell transplantation prevented scar thinning. LV dilatation and dysfunction while control animals developed scar thinning, significant LV dilatation accompanied by progressive deterioration in LV contractility. Transplantation of embryonic cardiomyocytes after extensive MI in a rat model attenuate LV dilatation, infarct thinning, and myocardial dysfunction. Still, many grafts remain isolated and do not differentiate into an adult phenotype, even when studied 2 months alfer grafting.
KW - Cells
KW - Heart failure
KW - Myocardial infarction
KW - Myocytes
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=0034952856&partnerID=8YFLogxK
U2 - 10.1006/jmcc.2000.1391
DO - 10.1006/jmcc.2000.1391
M3 - Article
AN - SCOPUS:0034952856
SN - 0022-2828
VL - 33
SP - 1321
EP - 1330
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 7
ER -