Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation

Duchenne muscular dystrophy (DMD) is a severe progressive muscle-wasting disorder caused by mutations in the dystrophin gene. Studies have shown that bone marrow cells transplanted into lethally irradiated mdx mice, the mouse model of DMD, can become part of skeletal muscle myofibers. Whether human...

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Bibliographic Details
Published in:The Journal of clinical investigation 2002-09, Vol.110 (6), p.807-814
Main Authors: Gussoni, Emanuela, Bennett, Richard R, Muskiewicz, Kristina R, Meyerrose, Todd, Nolta, Jan A, Gilgoff, Irene, Stein, James, Chan, Yiu-Mo, Lidov, Hart G, Bönnemann, Carsten G, Von Moers, Arpad, Morris, Glenn E, Den Dunnen, Johan T, Chamberlain, Jeffrey S, Kunkel, Louis M, Weinberg, Kenneth
Format: Article
Language:English
Subjects:
Adolescent
Animals
Biomedical research
Biopsy
Bone Marrow Cells - physiology
Bone Marrow Cells - ultrastructure
Bone Marrow Transplantation
Cell Nucleus - ultrastructure
Child
Dystrophin - genetics
Dystrophin - metabolism
Exons - genetics
Female
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Infant
Male
Muscle, Skeletal - cytology
Muscle, Skeletal - pathology
Muscular Dystrophy, Duchenne - genetics
Muscular Dystrophy, Duchenne - metabolism
Muscular Dystrophy, Duchenne - pathology
Severe Combined Immunodeficiency - therapy
Time Factors
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Summary:Duchenne muscular dystrophy (DMD) is a severe progressive muscle-wasting disorder caused by mutations in the dystrophin gene. Studies have shown that bone marrow cells transplanted into lethally irradiated mdx mice, the mouse model of DMD, can become part of skeletal muscle myofibers. Whether human marrow cells also have this ability is unknown. Here we report the analysis of muscle biopsies from a DMD patient (DMD-BMT1) who received bone marrow transplantation at age 1 year for X-linked severe combined immune deficiency and who was diagnosed with DMD at age 12 years. Analysis of muscle biopsies from DMD-BMT1 revealed the presence of donor nuclei within a small number of muscle myofibers (0.5-0.9%). The majority of the myofibers produce a truncated, in-frame isoform of dystrophin lacking exons 44 and 45 (not wild-type). The presence of bone marrow-derived donor nuclei in the muscle of this patient documents the ability of exogenous human bone marrow cells to fuse into skeletal muscle and persist up to 13 years after transplantation.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci0216098