[Dystrophin expression and pathology of diaphragm muscles of mdx mice after xenogenic bone marrow stem cell transplantation].
OBJECTIVE
To investigate the effect of bone marrow stem cell transplantation (BMT) on the diaphragm muscles of mdx mice, a mouse model of Duchenne muscular dystrophy (DMD).


METHODS
The bone marrow-derived stem cells form male SD rats was transplanted through the tail vein into 18 female 8-week-old mdx mice, which were sacrificed at 4, 8 and 12 weeks after BMT (6 at each time point), respectively. The diaphragm muscles of the mice were subjected to HE staining, immunofluorescence detection of dystrophin, reverse transcription (RT)-PCR analysis of dystrophin mRNA transcripts and PCR analysis of Sry (sex-determining region on the Y chromosome) gene, with age-matched female C57 mice and untreated mdx mice as the controls.


RESULTS
The proportion of centrally nucleated fibers (CNF) in the diaphragm muscle of the recipient mdx mice was (15.58+/-0.91) %, (12.50+/-1.87) % and (10.17+/-1.17) % at 4, 8 and 12 weeks after BMT, respectively, significantly smaller than that of untreated mdx mice [(19.5+/-1.87) %], and the fibers after BMT showed less inflammatory infiltration. Compared with the untreated mice, the recipient mdx mice showed green fluorescence on significantly more diaphragm muscle cell membranes [with the proportion of dystrophin-positive fibers of (1.00+/-0.32) %, (6.00+/-1.05) % and (11.92+/-1.11) % at 4, 8, and 12 weeks after BMT]. RT-PCR of dystrophin mRNA also demonstrated significantly higher relative levels of dystrophin in the recipient mdx mice (0.19+/-0.05, 0.26+/-0.06 and 0.36+/-0.04 at 4, 8 and 12 weeks after BMT) than in untreated mdx mice, and Sry gene was present in the recipient mice.


CONCLUSIONS
BMT can partially restore dystrophin expression and ameliorate the pathology in the diaphragm muscles of mdx mice, and has great potential to produce general therapeutic effect in patients with DMD.
Zhang
Ya-ni
YN
Department of Neurology, First Hospital of Sun Yat-sen University, Guangzhou 510080, China. zhangyanimonica@yahoo.com.cn
Zhang
Cheng
C
Yu
Mei-juan
MJ
Wang
Shu-hui
SH
Li
Mei-shan
MS
Huang
Hui
H
Xiong
Fu
F
Feng
Shan-wei
SW
Liu
Tai-yun
TY
Lu
Xi-lin
XL
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D003964:Diaphragm / Q000378:metabolism* / Q000473:pathology; D016189:Dystrophin / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous
D016189:Dystrophin