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.
abstract: 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.
authors.affiliation: Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tambara
authors.forename: Goditha U
authors.initials: GU
authors.lastname: Premaratne
authors.forename: Genichi
authors.initials: G
authors.lastname: Sakaguchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanemitsu
authors.forename: Xue
authors.initials: X
authors.lastname: Lin
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: Yu
authors.initials: Y
authors.lastname: Kimura
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Masashi
authors.initials: M
authors.lastname: Komeda
mesh_terms: 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
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; D020100:Hydrogels; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D005780:Gelatin