Administration of control-released hepatocyte growth factor enhances the efficacy of skeletal myoblast transplantation in rat infarcted hearts by greatly increasing both quantity and quality of the graft.
BACKGROUND
We investigated whether simultaneous administration of control-released hepatocyte growth factor (HGF) enhances the efficacy of skeletal myoblast (SM) transplantation (Tx) through its antiapoptotic, angiogenic, and antifibrotic effects in myocardial infarction (MI).


RESULTS
Forty-eight Lewis rats with chronic MI were divided into 4 groups. In Group I (n=14), neonatal SMs (5 x 10(6)) were transplanted in the MI area with a gelatin sheet incorporating 40 microg (1 g/L) of HGF applied. Group II (n=14) had SM Tx and placement of a saline sheet. Groups III (n=10) and IV (n=10) had culture medium injection plus HGF and saline sheet application, respectively. Four rats each from Groups I and II were sacrificed at day 1 for TUNEL assay on donor SMs. The percentage of TUNEL-positive donor cells was much lower in Group I than in Group II (P<0.05). At 4 weeks, in Group I, left ventricular diastolic dimension was smallest in echocardiography, end-systolic elastance was highest, and tau was the lowest (both P<0.0005 in ANOVA) in cardiac catheterization. Vascular density inside the graft was higher in Group I than in Group II (P<0.0001). The percentage of fibrotic area inside the graft was smaller in Group I than in Group II (P<0.001). The graft volume as estimated by fast skeletal myosin heavy chain-positive areas was approximately 7-fold larger in Group I than in Group II (P<0.0001).


CONCLUSIONS
In SM Tx, HGF can greatly increase the graft volume and vascularity and reduce fibrosis inside the graft, which enhances the efficacy of SM Tx to infarcted hearts.
Tambara
Keiichi
K
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Premaratne
Goditha U
GU
Sakaguchi
Genichi
G
Kanemitsu
Naoki
N
Lin
Xue
X
Nakajima
Hiroyuki
H
Sakakibara
Yutaka
Y
Kimura
Yu
Y
Yamamoto
Masaya
M
Tabata
Yasuhiko
Y
Ikeda
Tadashi
T
Komeda
Masashi
M
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002417:Cattle; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005355:Fibrosis; D005780:Gelatin; D006082:Graft Enhancement, Immunologic; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D020100:Hydrogels; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology; D032446:Myoblasts / Q000637:transplantation*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D009929:Organ Size; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D014463:Ultrasonography; D016277:Ventricular Function, Left
D003692:Delayed-Action Preparations; D004343:Drug Implants; D020100:Hydrogels; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D005780:Gelatin