1. ¹Program in Transplantation Biology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
2. ²Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
3. ³Department of Neurology, University of Washington, Seattle, Washington, USA
4. ⁴Department of Medicine, University of Washington, Seattle, Washington, USA

Correspondence: Rainer Storb, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., D1-100, Seattle, Washington 98109-1024, USA. E-mail: rstorb@fhcrc.org; Stephen J. Tapscott, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., C3-168, Seattle, Washington 98109-1024, USA. E-mail: stapscot@fhcrc.org

Received 31 January 2008; Accepted 16 April 2008; Published online 27 May 2008.

Abstract

Duchenne Muscular Dystrophy (DMD) is the most common and severe form of muscular dystrophy in humans. The goal of myogenic stem cell transplant therapy for DMD is to increase dystrophin expression in existing muscle fibers and to provide a source of stem cells for future muscle generation. Although syngeneic myogenic stem cell transplants have been successful in mice, allogeneic transplants of myogenic stem cells were ineffective in several human trials. To determine whether allogeneic muscle progenitor cells can be successfully transplanted in an immune-tolerant recipient, we induced immune tolerance in two DMD-affected (cxmd) dogs through hematopoietic cell transplantation (HCT). Injection of freshly isolated muscle-derived cells from the HCT donor into either fully or partially chimeric xmd recipients restored dystrophin expression up to 6.48% of wild-type levels, reduced the number of centrally located nuclei, and improved muscle structure. Dystrophin expression was maintained for at least 24 weeks. Taken together, these data indicate that immune tolerance to donor myoblasts provides an important platform from which to further improve myoblast transplantation, with the goal of restoring dystrophin expression to patients with DMD.