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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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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469349/
https://www.ncbi.nlm.nih.gov/pubmed/34572277
http://dx.doi.org/10.3390/biomedicines9091089
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author 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
author_facet 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
author_sort Park, Sang Eon
collection PubMed
description 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.
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spelling pubmed-84693492021-09-27 Wharton’s Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499 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 Biomedicines Article 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. MDPI 2021-08-26 /pmc/articles/PMC8469349/ /pubmed/34572277 http://dx.doi.org/10.3390/biomedicines9091089 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Wharton’s Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499
title Wharton’s Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499
title_full Wharton’s Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499
title_fullStr Wharton’s Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499
title_full_unstemmed Wharton’s Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499
title_short Wharton’s Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499
title_sort wharton’s jelly-derived mesenchymal stem cells reduce fibrosis in a mouse model of duchenne muscular dystrophy by upregulating microrna 499
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469349/
https://www.ncbi.nlm.nih.gov/pubmed/34572277
http://dx.doi.org/10.3390/biomedicines9091089
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