title: Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation.
abstract: 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.
authors.affiliation: Division of Genetics, Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Gussoni
authors.forename: Richard R
authors.initials: RR
authors.lastname: Bennett
authors.forename: Kristina R
authors.initials: KR
authors.lastname: Muskiewicz
authors.forename: Todd
authors.initials: T
authors.lastname: Meyerrose
authors.forename: Jan A
authors.initials: JA
authors.lastname: Nolta
authors.forename: Irene
authors.initials: I
authors.lastname: Gilgoff
authors.forename: James
authors.initials: J
authors.lastname: Stein
authors.forename: Yiu-Mo
authors.initials: YM
authors.lastname: Chan
authors.forename: Hart G
authors.initials: HG
authors.lastname: Lidov
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Bönnemann
authors.forename: Arpad
authors.initials: A
authors.lastname: Von Moers
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Morris
authors.forename: Johan T
authors.initials: JT
authors.lastname: Den Dunnen
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Chamberlain
authors.forename: Louis M
authors.initials: LM
authors.lastname: Kunkel
authors.forename: Kenneth
authors.initials: K
authors.lastname: Weinberg
mesh_terms: D000293:Adolescent; D000818:Animals; D001706:Biopsy; D001854:Bone Marrow Cells / Q000502:physiology* / Q000648:ultrastructure; D016026:Bone Marrow Transplantation; D002467:Cell Nucleus / Q000648:ultrastructure; D002648:Child; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016511:Severe Combined Immunodeficiency / Q000628:therapy; D013997:Time Factors
chemical_list: D016189:Dystrophin