Wharton’s Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499

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 we...

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Bibliographic Details
Published in:Biomedicines 2021-08, Vol.9 (9), p.1089
Main 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
Format: Article
Language:English
Subjects:
Accreditation
Animal models
Antibodies
Apoptosis
Clinical trials
Creatine
Creatine kinase
Duchenne muscular dystrophy
Duchenne's muscular dystrophy
Fibrosis
Immunohistochemistry
Injection
Intravenous administration
Laboratory animals
Manufacturers
Medical research
Mesenchymal stem cells
microRNA-499-5p
MicroRNAs
miRNA
Muscle strength
Muscular dystrophy
Musculoskeletal system
Rodents
Skeletal muscle
skeletal muscle fibrosis
Stem cell transplantation
Stem cells
Western blotting
Wharton’s jelly-derived mesenchymal stem cell
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Summary: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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines9091089