Longer preservation of cardiac performance by sheet-shaped myoblast implantation in dilated cardiomyopathic hamsters.
OBJECTIVE
Cell therapy is a promising strategy for ischemic cardiomyopathy. However, the direct injection method has limitations for generalized cell delivery, especially in dilated cardiomyopathy (DCM). We hypothesized that a sheet-shaped myoblast graft would be superior to direct injection for improving cardiac performance in DCM.


METHODS
Male 27-week-old BIO TO-2 (DCM) hamsters that showed moderate cardiac remodeling were used as recipients. Myoblasts isolated from BIO F1B hamsters were cultured on dishes coated with poly(N-isopropylacrylamide), a temperature-responsive polymer, and spontaneously detached as a sheet-shaped graft at 20 degrees C without enzymatic treatment. Three different therapies were conducted: (1) sheet-shaped myoblast graft implantation (S group, n=29); (2) myoblast injection (M group, n=28); and (3) sham operation (C group, n=28). In the S group, two sheet-shaped myoblast grafts were implanted on the left ventricle (LV) wall, and in the M group, myoblasts were injected into the right ventricle (RV) and LV walls.


RESULTS
After the sheet-shaped myoblast grafts were implanted, echocardiography demonstrated that the dilated LV dimension was significantly reduced, whereas the hearts in other groups showed a progression of LV dilation. The fractional shortening in the M and C groups decreased significantly while that in the S group was maintained at the preoperative level for 3 months after the operation. Histological examination demonstrated that in the S group, the LV wall thickness was increased, with viable myoblasts, and myocardial fibrosis was decreased compared with the other groups. Immunohistochemical staining demonstrated alpha-sarcoglycan and beta-sarcoglycan expression on the basement membrane of the cardiomyocytes in the S group but not in the other groups. The life expectancy was significantly prolonged in the S group.


CONCLUSIONS
Sheet-shaped myoblast graft implantation improved cardiac performance and prolonged life expectancy, associated with a reduction in myocardial fibrosis and re-organization of the cytoskeletal proteins in DCM hamsters. Thus, sheet-shaped autologous myoblast graft implantation may induce restoration of the heart in DCM.
Kondoh
Haruhiko
H
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Sawa
Yoshiki
Y
Miyagawa
Shigeru
S
Sakakida-Kitagawa
Satoru
S
Memon
Imran A
IA
Kawaguchi
Naomasa
N
Matsuura
Nariaki
N
Shimizu
Tatsuya
T
Okano
Teruo
T
Matsuda
Hikaru
H
D000818:Animals; D001485:Basement Membrane / Q000737:chemistry; D002306:Cardiac Volume; D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D006224:Cricetinae; D004452:Echocardiography; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D032446:Myoblasts / Q000637:transplantation*; D009200:Myocardial Contraction; D049031:Sarcoglycans / Q000032:analysis; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D049031:Sarcoglycans