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

Circulation. 2005 Aug 30;112(9 Suppl):I129-34. doi: 10.1161/CIRCULATIONAHA.104.526293.


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 terms

  • 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


  • Delayed-Action Preparations
  • Drug Implants
  • Hydrogels
  • Recombinant Proteins
  • Hepatocyte Growth Factor
  • Gelatin