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Hematopoietic cell transplantation provides an immune-tolerant platform for myoblast transplantation in dystrophic dogs.

Parker, Maura H and Kuhr, Christian and Tapscott, Stephen J and Storb, Rainer (2008) Hematopoietic cell transplantation provides an immune-tolerant platform for myoblast transplantation in dystrophic dogs. Molecular therapy : the journal of the American Society of Gene Therapy, 16 (7). pp. 1340-1346. ISSN 1525-0024

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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.

Item Type: Article or Abstract
Additional Information: This article is available to subscribers only via the URL above.
DOI: 10.1038/mt.2008.102
PubMed ID: 18500253
PMCID: PMC2536604
Grant Numbers: P30 CA015704-34, P01 CA078902-100004, P30 DK056465-099007, U54 HD047175-05
Keywords or MeSH Headings: Animals; Dogs; *Hematopoietic Stem Cell Transplantation; Immune Tolerance; Immunosuppression/*methods; Muscular Dystrophy, Duchenne/*surgery; Myoblasts/immunology/*transplantation
Subjects: Organisms > Model organisms
Therapeutics > Transplantation > Stem Cell transplantation
Diseases > Hereditary Diseases
Depositing User: Library Staff
Date Deposited: 14 Aug 2008 23:09
Last Modified: 14 Feb 2012 14:42

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