Transplantation of elastin-secreting myoblast sheets improves cardiac function in infarcted rat heart.
Myoblast sheet transplantation for cardiac failure is a promising therapy to enhance cardiac function via paracrine mechanism. However, their efficacies of treatment showed a gradual decline. The gene modification of the implanted myoblast is important in improving the long-term results of the treatment. Elastin fiber enhances the extensibility of the infarcted wall and can prevent left ventricular dilation. We therefore hypothesized that the elastin gene modification of the implanted myoblast could strengthen and maintain the long-term improvement effects of cardiac function. In this study, we evaluated long-term follow-up benefits of functional myoblast sheets that secrete elastin in an infarcted model. The animal models were divided into three groups: a group transplanted with nontransfected, wild-type, skeletal myoblast-type sheets (WT-rSkM); group transplanted with myoblast sheets that secreted elastin fragments (ELN-rSkM); and a control group (ligation only). Cardiac function was examined by echocardiography, and cardiac remodeling after infarction was evaluated by histological examination. The cardiac function was significantly improved and the left ventricle end-diastolic dimensions were significantly reduced in the ELN-rSkM group. Histological analysis showed that left ventricular remodeling was attenuated in the ELN-rSkM group and that elastic fiber was formed in the epicardial area of ELN-rSkM group. The functionalization of myoblast sheet by elastin gene transfer showed the long-term improvement of cardiac function. Expressed recombinant elastin fiber prevented the dilation of the left ventricular chamber after myocardial infarction. The functional myoblast sheet transplantation maintained the treatment effect by the paracrine effect of myoblast and the formed recombinant elastin.
Department of Molecular pathology, Osaka University Graduate School of Medicine, Division of Health Sciences, 1-7 Yamada-oka, Suita, Osaka 565-0871, Japan.
Ayako
A
Uchinaka
Naomasa
N
Kawaguchi
Yoshinosuke
Y
Hamada
Shigeru
S
Miyagawa
Atsuhiro
A
Saito
Seiji
S
Mori
Yoshiki
Y
Sawa
Nariaki
N
Matsuura
D000818:Animals; D004452:Echocardiography; D004549:Elastin / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy*; D009206:Myocardium; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D020127:Recovery of Function; D014184:Transplantation, Homologous
D011994:Recombinant Proteins; D004549:Elastin