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 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.
Gussoni
Emanuela
E
Division of Genetics, Children's Hospital, Boston, Massachusetts 02115, USA.
Bennett
Richard R
RR
Muskiewicz
Kristina R
KR
Meyerrose
Todd
T
Nolta
Jan A
JA
Gilgoff
Irene
I
Stein
James
J
Chan
Yiu-Mo
YM
Lidov
Hart G
HG
Bönnemann
Carsten G
CG
Von Moers
Arpad
A
Morris
Glenn E
GE
Den Dunnen
Johan T
JT
Chamberlain
Jeffrey S
JS
Kunkel
Louis M
LM
Weinberg
Kenneth
K
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
D016189:Dystrophin