Does the functional efficacy of skeletal myoblast transplantation extend to nonischemic cardiomyopathy?

Circulation. 2004 Sep 21;110(12):1626-31. doi: 10.1161/01.CIR.0000142861.55862.15. Epub 2004 Sep 13.

Abstract

Background: The benefits of skeletal myoblast (SM) transplantation on infarcted myocardium have been investigated extensively; however, little is known about its effects in nonischemic cardiomyopathy models. To address this issue, we tested SM transplantation in CHF147 Syrian hamsters, a strain characterized by a delta-sarcoglycan deficiency that phenotypically features the human setting of primary dilated cardiomyopathy.

Methods and results: Cell culture techniques were used to prepare approximately 5x10(6) muscle cells from autologous tibialis anterior muscle, of which 50% were SMs (desmin staining). The cells were injected in 6 sites across the left ventricular wall (n=14). Control animals (n=12) received equivalent volumes of culture medium. Left ventricular systolic function was assessed in a blinded fashion from 2D echocardiographic left ventricular fractional area change, before transplantation, and 4 weeks later. Explanted hearts were processed for the detection of myotubes and quantification of fibrosis. Baseline functional data did not differ between the 2 groups. Four weeks after transplantation, 6 of the 10 surviving grafted hamsters were improved compared with 0 of the 8 survivors of the control group. This translated into a 6% decrease in fractional area change in controls compared with a 24% increase in cell-transplanted hamsters (P=0.001). Engrafted myotubes were consistently detected in all SM transplanted hearts by immunohistochemistry, whereas fibrosis was not worsened by cell injections.

Conclusions: These data suggest that the functional benefits of SM transplantation might extend to nonischemic cardiomyopathy.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathy, Dilated / genetics
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / physiopathology
  • Cardiomyopathy, Dilated / therapy*
  • Cells, Cultured / transplantation
  • Cricetinae
  • Female
  • Fibrosis
  • Heart Ventricles / physiopathology
  • Injections
  • Male
  • Mesocricetus
  • Muscle, Skeletal / cytology*
  • Myoblasts / transplantation*
  • Myocardium / pathology
  • Random Allocation
  • Sarcoglycans / deficiency
  • Single-Blind Method
  • Transplantation, Heterotopic
  • Ventricular Function, Left

Substances

  • Sarcoglycans