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


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.
Pouly
Julia
J
INSERM U582, Institute of Myology, Groupe Hospitalier Pitié-Salpétrière, 47 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France. j.pouly@myologie.chups.jussieu.fr
Hagège
Albert A
AA
Vilquin
Jean-Thomas
JT
Bissery
Alvine
A
Rouche
Andrée
A
Bruneval
Patrick
P
Duboc
Denis
D
Desnos
Michel
M
Fiszman
Marc
M
Fromes
Yves
Y
Menasché
Philippe
P
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002478:Cells, Cultured / Q000637:transplantation; D006224:Cricetinae; D005260:Female; D005355:Fibrosis; D006352:Heart Ventricles / Q000503:physiopathology; D007267:Injections; D008297:Male; D008647:Mesocricetus; D018482:Muscle, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000637:transplantation*; D009206:Myocardium / Q000473:pathology; D011897:Random Allocation; D049031:Sarcoglycans / Q000172:deficiency; D016037:Single-Blind Method; D016042:Transplantation, Heterotopic; D016277:Ventricular Function, Left
D049031:Sarcoglycans