Wharton's Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499.
Sang Eon ParkJang Bin JeongShin Ji OhSun Jeong KimHyeongseop KimAlee ChoiSuk-Joo ChoiSoo-Young OhGyu Ha RyuJeehun LeeHong Bae JeonJong Wook ChangPublished in: Biomedicines (2021)
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.
Keyphrases
- duchenne muscular dystrophy
- mesenchymal stem cells
- skeletal muscle
- high fat diet induced
- umbilical cord
- muscular dystrophy
- mouse model
- clinical trial
- bone marrow
- poor prognosis
- idiopathic pulmonary fibrosis
- cell proliferation
- wild type
- south africa
- high dose
- metabolic syndrome
- pulmonary embolism
- placebo controlled
- double blind