title: Therapeutic effects of mouse adipose-derived stem cells and losartan in the skeletal muscle of injured mdx mice.
abstract: Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder caused by mutations in the dystrophin gene. Adipose-derived stem cells (ASCs) are an attractive source of cells for stem cell therapy. Losartan has been reported to improve ASC transplantation in injured mouse muscles. In the present study, we investigated whether the combined treatment of losartan and ASCs in the injured muscles of mdx mice improves regeneration. The combined treatment of ASCs and losartan remarkably improved muscle regeneration and induced muscle hypertrophy. In addition, ASCs and losartan treatment downregulated transforming growth factor-β and inhibited muscle fibrosis. We observed cells coexpressing green fluorescent protein (GFP) and dystrophin in the muscle samples of mice transplanted with GFP-positive ASCs. In the coculture in vitro experiment, we also observed that the GFP ASCs differentiated into dystrophin-expressing myotubes. The present study shows that the combination of transplanted ASCs and treatment with losartan ameliorated muscle fibrosis and improved muscle regeneration in injured mdx mice. Thus, we suggest that combined treatment with losartan and ASCs could help to improve muscle regeneration in the muscles of injured patients, including DMD patients.
authors.affiliation: College of Veterinary Medicine, Kyungpook National University, Daegu City, Republic of Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Lee
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Kim
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Lee
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Myeong-Mi
authors.initials: MM
authors.lastname: Lee
authors.forename: Meeyul
authors.initials: M
authors.lastname: Hwang
authors.forename: Choong-Yong
authors.initials: CY
authors.lastname: Kim
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Kyu-Shik
authors.initials: KS
authors.lastname: Jeong
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D019808:Losartan