Flk-1+ adipose-derived mesenchymal stem cells differentiate into skeletal muscle satellite cells and ameliorate muscular dystrophy in mdx mice.
Duchenne muscular dystrophy (DMD) is a severe hereditary disease characterized by the absence of dystrophin on the sarcolemma of muscle fiber. This absence results in widespread muscle damage and satellite cell activation. After depletion of the satellite cell pool, skeletal muscle is then invariably replaced by connective tissue, leading to progressive muscle weakness. Herein, we isolated Flk-1(+) mesenchymal stem cells (MSCs) from adult adipose tissue and induced them to differentiate into skeletal muscle cells in culture. Within mdx mice, an animal model of DMD, adipose tissue-derived Flk-1(+) MSCs (AD-MSCs) homed to and differentiated into cells that repaired injured muscle tissue. This repair correlated with reconstitution of dystrophin expression on the damaged fibers. Flk-1(+) AD-MSCs also differentiated into muscle satellite cells. This differentiation may have accounted for long-term reconstitution. These cells also differentiated into endothelial cells, thereby possibly improving fiber regeneration as a result of the induced angiogenesis. Therefore, Flk-1(+) AD-MSC transplants may repair muscular dystrophy.
Liu
Yanning
Y
Institute of Basic Medical Sciences & School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Yan
Xi
X
Sun
Zhao
Z
Chen
Bin
B
Han
Qin
Q
Li
Jing
J
Zhao
Robert Chunhua
RC
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D054715:Cardiotoxins; D002454:Cell Differentiation; D002478:Cells, Cultured; D016189:Dystrophin / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018101:Mice, Inbred mdx; D009137:Muscular Dystrophy, Animal / Q000139:chemically induced / Q000473:pathology*; D018919:Neovascularization, Physiologic; D010641:Phenotype; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D054715:Cardiotoxins; D016189:Dystrophin; D040301:Vascular Endothelial Growth Factor Receptor-2