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

Authors
SE Park, JB Jeong, SJ Oh et al

Lab
Sungkyunkwan University School of Medicine, Seoul, Korea

Journal
Biomedicines

Abstract
The aim of this study was to evaluate the therapeutic effects and mechanisms of WhartonÕs jelly-derived mesenchymal stem cells (WJ-MSCs) in an animal model of Duchenne muscular dystrophy (DMD). Mdx mice (3Ð5 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 TGFbetaR 1 and 3. Thus, WJ-MSCs may represent novel allogeneic Òoff-the-shelfÓ cellular products for the treatment of DMD and possibly other muscle disorders.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)