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Circulation. 2004;110:1626-1631
Published online before print September 13, 2004, doi: 10.1161/01.CIR.0000142861.55862.15
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(Circulation. 2004;110:1626-1631.)
© 2004 American Heart Association, Inc.


Heart Failure

Does the Functional Efficacy of Skeletal Myoblast Transplantation Extend to Nonischemic Cardiomyopathy?

Julia Pouly, MD; Albert A. Hagège, MD, PhD; Jean-Thomas Vilquin, PharmD, PhD; Alvine Bissery, MSc; Andrée Rouche, MSc; Patrick Bruneval, MD, PhD; Denis Duboc, MD; Michel Desnos, MD; Marc Fiszman, PharmD, PhD; Yves Fromes, MD, PhD; Philippe Menasché, MD, PhD

From INSERM 582, Institute of Myology (J.P., J.-T.V., A.R., M.F., Y.F.); INSERM 633, Laboratoire d’Etude des Greffes et Prothèses Cardiaques, Hôpital Broussais (J.P., A.A.H., M.D., P.M.); Departments of Cardiovascular Surgery (J.P., P.M.) and Pathology (P.B.), Hôpital Européen Georges Pompidou; Department of Cardiology, Hôpital Européen Georges Pompidou (A.A.H., M.D.); University René Descartes (A.A.H., M.D., P.M.); Clinical Investigation Center, Assistance Publique des Hôpitaux de Paris/INSERM, Hôpital Européen Georges Pompidou (A.B.); and Department of Cardiology, Hôpital Cochin (D.D.), Paris, France.

Correspondence to Julia Pouly, MD, INSERM U582, Institute of Myology, Groupe Hospitalier Pitié-Salpétrière, 47 Boulevard de l’Hôpital, 75651 Paris Cedex 13, France. E-mail j.pouly{at}myologie.chups.jussieu.fr

Received May 26, 2004; revision received July 5, 2004; accepted July 15, 2004.

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 {approx}5x106 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.


Key Words: cardiomyopathy • heart failure • myoblasts, skeletal • tissue therapy




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