4.8 Article

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

Journal

CIRCULATION
Volume 110, Issue 12, Pages 1626-1631

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.CIR.0000142861.55862.15

Keywords

cardiomyopathy; heart failure; myoblasts, skeletal; tissue therapy

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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 approximate to5x10(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.

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