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- Title
Wharton's Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499.
- Authors
Park, Sang Eon; Jeong, Jang Bin; Oh, Shin Ji; Kim, Sun Jeong; Kim, Hyeongseop; Choi, Alee; Choi, Suk-joo; Oh, Soo-young; Ryu, Gyu Ha; Lee, Jeehun; Jeon, Hong Bae; Chang, Jong Wook
- Abstract
The aim of this study was to evaluate the therapeutic effects and mechanisms of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) in an animal model of Duchenne muscular dystrophy (DMD). Mdx mice (3–5 months old) were administered five different doses of WJ-MSCs through their tail veins. A week after injection, grip strength measurements, creatine kinase (CK) assays, immunohistochemistry, and western blots were performed for comparison between healthy mice, mdx control mice, and WJ-MSC-injected mdx mice. WJ-MSCs exerted dose-dependent multisystem therapeutic effects in mdx mice, by decreasing CK, recovering normal behavior, regenerating muscle, and reducing apoptosis and fibrosis in skeletal muscle. We also confirmed that miR-499-5p is significantly downregulated in mdx mice, and that intravenous injection of WJ-MSCs enhanced its expression, leading to anti-fibrotic effects via targeting TGFβR 1 and 3. Thus, WJ-MSCs may represent novel allogeneic "off-the-shelf" cellular products for the treatment of DMD and possibly other muscle disorders.
- Subjects
MESENCHYMAL stem cells; DUCHENNE muscular dystrophy; LABORATORY mice; ANIMAL disease models; MICRORNA
- Publication
Biomedicines, 2021, Vol 9, Issue 9, p1089
- ISSN
2227-9059
- Publication type
Article
- DOI
10.3390/biomedicines9091089