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  • Inherited Disease
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Matching host muscle and donor myoblasts for myosin heavy chain improves myoblast transfer therapy

Gene Therapy volume 7, pages 428–437 (2000)Cite this article

Abstract

Intensive efforts have been made to develop an effective therapy for Duchenne muscular dystrophy (DMD). Although myoblast transplantation has been found capable of transiently delivering dystrophin and improving the strength of the injected dystrophic muscle, this approach has been hindered by the immune rejection problems as well as the poor survival and limited spread of the injected cells. In the present study, we have investigated whether the careful selection of donor myoblasts and host muscle for the myosin heavy chain expression (MyHCs) plays a role in the success of myoblast transfer. Highly purified normal myoblasts derived from the m. soleus and m. gastrocnemius white of normal mice were transplanted into the m. soleus (containing 70% of type I fibers) and gastrocnemius white (100% of type II fibers) of dystrophin deficient mdx mice. At several time-points after injection (10, 20 and 30 days), the number of dystrophin-positive fibers was monitored and compared among the different groups. A significantly higher number and better persistence of dystrophin-positive myofibers were observed when the injected muscle and donor myoblasts expressed a similar MyHC in comparison with myoblast transfer between host muscle and donor myoblasts that were not matched for MyHC. These results suggest that careful matching between the injected myoblasts and injected muscle for the MyHC expression can improve the efficiency of myoblast-mediated gene transfer to skeletal muscle.

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Acknowledgements

We wish to thank Marcelle Pellerin and Ryan Pruchnic for their technical help and Megan Mowry, Dana Och and Sarah Martin for assistance with the manuscript. We also thank Dr LM Kunkel for the rabbit anti-dystrophin antibody (6–10). This work was supported by grants to Dr Johnny Huard from the Parent Project (USA), The Muscular Dystrophy Association (USA), the National Institutes of Health (NIH), Children's Hospital of Pittsburgh, and University of Pittsburgh.

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  1. Department of Orthopaedic Surgery and Molecular Genetics and Biochemistry, Growth and Development Laboratory, Musculoskeletal Research Center, Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, PA 15261, USA

    Z Qu & J Huard

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Qu, Z., Huard, J. Matching host muscle and donor myoblasts for myosin heavy chain improves myoblast transfer therapy. Gene Ther 7, 428–437 (2000). https://doi.org/10.1038/sj.gt.3301103

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