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

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2021 Sep 28

PMID 34572277

Citations 9

Authors

Sang Eon Park

Jang Bin Jeong

Shin Ji Oh

Sun Jeong Kim

Hyeongseop Kim

Alee Choi

Suk-Joo Choi

Soo-Young Oh

Gyu Ha Ryu

Jeehun Lee

Hong Bae Jeon

Jong Wook Chang

Affiliations

Soon will be listed here.

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.

Citing Articles

Safety and Tolerability of Wharton's Jelly-Derived Mesenchymal Stem Cells for Patients With Duchenne Muscular Dystrophy: A Phase 1 Clinical Study.

Lee J, Park S, Kim M, Kim H, Kwon J, Jeon H J Clin Neurol. 2025; 21(1):40-52.

PMID: 39778566 PMC: 11711273. DOI: 10.3988/jcn.2024.0299.

Anti-necroptotic effects of human Wharton's jelly-derived mesenchymal stem cells in skeletal muscle cell death model via secretion of GRO-α.

Park S, Kwon S, Kim S, Jeong J, Kim M, Choi S PLoS One. 2024; 19(12):e0313693.

PMID: 39621655 PMC: 11611217. DOI: 10.1371/journal.pone.0313693.

Identification of miR-1 and miR-499 in chronic atrial fibrillation by bioinformatics analysis and experimental validation.

Chen X, Zhang Y, Meng H, Chen G, Ma Y, Li J Front Cardiovasc Med. 2024; 11:1400643.

PMID: 39221422 PMC: 11361948. DOI: 10.3389/fcvm.2024.1400643.

Glutaminase-1 inhibition alleviates senescence of Wharton's jelly-derived mesenchymal stem cells via senolysis.

Lee E, Kim S, Jeon S, Chung S, Park S, Kim J Stem Cells Transl Med. 2024; 13(9):873-885.

PMID: 39120480 PMC: 11386220. DOI: 10.1093/stcltm/szae053.

The Role of MicroRNA in the Pathogenesis of Duchenne Muscular Dystrophy.

Kielbowski K, Bakinowska E, Procyk G, Zietara M, Pawlik A Int J Mol Sci. 2024; 25(11).

PMID: 38892293 PMC: 11172814. DOI: 10.3390/ijms25116108.

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