[Mesenchymal stem cells transplanted in mdx mice differentiate into myocytes and express dystrophin/utrophin].
OBJECTIVE
To investigate the differentiation of rat bone marrow mesenchymal stem cells (MSCs) into myocytes and their expression of dystrophin/utrophin after transplantation in mdx mice.


METHODS
BrdU-labeled fifth-passage rat MSCs were transplanted in mdx mice with previous total body gamma irradiation (7 Gy). At 4, 8, 12 and 16 weeks after the transplantation, the mice were sacrificed to detect dystrophin/BrdU and utrophin expressions in the gastrocnemius muscle using immunofluorescence assay, RT-PCR and Western blotting. Five normal C57 BL/6 mice and 5 mdx mice served as the positive and negative controls, respectively.


RESULTS
Four weeks after MSC transplantation, less than 1% of the muscle fibers of the mdx mice expressed dystrophin, which increased to 15% at 16 weeks. Donor-derived nuclei were detected in both single and clusters of dystrophin-positive fibers. Some BrdU-positive nuclei were centrally located, and some peripherally within myofibers. Utrophin expression decreased over time after transplantation.


CONCLUSIONS
The myofibers of mdx mice with MSC transplantation express dystrophin, which is derived partially from the transplanted MSCs. Dystrophin expression from the transplanted MSCs partially inhibits the upregulation of utrophin in mdx mouse muscle, showing a complementary relation between them.
Feng
Shan-wei
SW
Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Center for Stem Cell Biology and Tissue Engineering, Guangzhou 510080, China.
Zhang
Cheng
C
Lu
Xi-lin
XL
Liu
Tai-yun
TY
Li
Cai-ming
CM
Yao
Xiao-li
XL
Yu
Mei-juan
MJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D049411:Utrophin / Q000378:metabolism
D016189:Dystrophin; D049411:Utrophin