Reference - Detail
|Author||Tambara K, Premaratne GU, Sakaguchi G, Kanemitsu N, Lin X, Nakajima H, Sakakibara Y, Kimura Y, Yamamoto M, Tabata Y, Ikeda T, Komeda M.|
|Title||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).
METHODS AND 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.
|MeSH||Animals Animals, Newborn Apoptosis Cattle Delayed-Action Preparations Drug Implants Fibrosis Gelatin Graft Enhancement, Immunologic Hepatocyte Growth Factor / administration & dosage Hepatocyte Growth Factor / therapeutic use* Hydrogels Male Muscle, Skeletal / cytology Myoblasts / transplantation* Myocardial Infarction / diagnostic imaging Myocardial Infarction / drug therapy Myocardial Infarction / pathology Myocardial Infarction / surgery* Organ Size Rats Rats, Inbred Lew Recombinant Proteins / administration & dosage Recombinant Proteins / therapeutic use Ultrasonography Ventricular Function, Left|
|WOS Category||CARDIAC & CARDIOVASCULAR SYSTEMS PERIPHERAL VASCULAR DISEASE|