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Heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy

Duchenne muscular dystrophy (DMD) is a progressive muscle disease, characterized by mutations in the X-linked dystrophin, that has several therapeutic options but no curative treatment. Transplantation of muscle progenitor cells for treatment of DMD has been widely investigated; however, its applica...

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Autores principales: Lu, Aiping, Guo, Ping, Wang, Liang, Tseng, Chieh, Huard, Matthieu, Allen, Chris, McCarrick-Walmsley, Ruth, Whitney, Kaitlyn E., Huard, Johnny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184587/
https://www.ncbi.nlm.nih.gov/pubmed/32341395
http://dx.doi.org/10.1038/s41598-020-64042-z
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author Lu, Aiping
Guo, Ping
Wang, Liang
Tseng, Chieh
Huard, Matthieu
Allen, Chris
McCarrick-Walmsley, Ruth
Whitney, Kaitlyn E.
Huard, Johnny
author_facet Lu, Aiping
Guo, Ping
Wang, Liang
Tseng, Chieh
Huard, Matthieu
Allen, Chris
McCarrick-Walmsley, Ruth
Whitney, Kaitlyn E.
Huard, Johnny
author_sort Lu, Aiping
collection PubMed
description Duchenne muscular dystrophy (DMD) is a progressive muscle disease, characterized by mutations in the X-linked dystrophin, that has several therapeutic options but no curative treatment. Transplantation of muscle progenitor cells for treatment of DMD has been widely investigated; however, its application is hindered by limited cell survival due to the harmful dystrophic microenvironment. An alternative approach to utilize progenitor cells and circulatory factors and to improve the dystrophic muscle pathology and microenvironment is through parabiotic pairing, where mice are surgically sutured to create a joint circulatory system. Parabiotic mice were generated by surgically joining wild type (WT) mice expressing green fluorescent protein (GFP) with mdx mice. These mice developed a common circulation (approximately 50% green cells in the blood of mdx mice) 2-weeks after parabiotic pairing. We observed significantly improved dystrophic muscle pathology, including decreased inflammation, necrotic fibers and fibrosis in heterogenetic parabionts. Importantly, the GFP + cells isolated from the mdx mice (paired with GFP mice) underwent myogenic differentiation in vitro and expressed markers of mesenchymal stem cells and macrophages, which may potentially be involved in the improvement of dystrophic muscle pathology. These observations suggest that changing the dystrophic microenvironment can be a new approach to treat DMD.
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spelling pubmed-71845872020-04-29 Heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy Lu, Aiping Guo, Ping Wang, Liang Tseng, Chieh Huard, Matthieu Allen, Chris McCarrick-Walmsley, Ruth Whitney, Kaitlyn E. Huard, Johnny Sci Rep Article Duchenne muscular dystrophy (DMD) is a progressive muscle disease, characterized by mutations in the X-linked dystrophin, that has several therapeutic options but no curative treatment. Transplantation of muscle progenitor cells for treatment of DMD has been widely investigated; however, its application is hindered by limited cell survival due to the harmful dystrophic microenvironment. An alternative approach to utilize progenitor cells and circulatory factors and to improve the dystrophic muscle pathology and microenvironment is through parabiotic pairing, where mice are surgically sutured to create a joint circulatory system. Parabiotic mice were generated by surgically joining wild type (WT) mice expressing green fluorescent protein (GFP) with mdx mice. These mice developed a common circulation (approximately 50% green cells in the blood of mdx mice) 2-weeks after parabiotic pairing. We observed significantly improved dystrophic muscle pathology, including decreased inflammation, necrotic fibers and fibrosis in heterogenetic parabionts. Importantly, the GFP + cells isolated from the mdx mice (paired with GFP mice) underwent myogenic differentiation in vitro and expressed markers of mesenchymal stem cells and macrophages, which may potentially be involved in the improvement of dystrophic muscle pathology. These observations suggest that changing the dystrophic microenvironment can be a new approach to treat DMD. Nature Publishing Group UK 2020-04-27 /pmc/articles/PMC7184587/ /pubmed/32341395 http://dx.doi.org/10.1038/s41598-020-64042-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lu, Aiping
Guo, Ping
Wang, Liang
Tseng, Chieh
Huard, Matthieu
Allen, Chris
McCarrick-Walmsley, Ruth
Whitney, Kaitlyn E.
Huard, Johnny
Heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy
title Heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy
title_full Heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy
title_fullStr Heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy
title_full_unstemmed Heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy
title_short Heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy
title_sort heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184587/
https://www.ncbi.nlm.nih.gov/pubmed/32341395
http://dx.doi.org/10.1038/s41598-020-64042-z
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