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Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model
Amyotrophic Lateral Sclerosis (ALS) is the most common adult motor neuron disease, with a poor prognosis, a highly unmet therapeutic need, and a burden on health care costs. Hitherto, strategies aimed at protecting motor neurons have missed or modestly delayed ALS due to a failure in countering the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093513/ https://www.ncbi.nlm.nih.gov/pubmed/37048088 http://dx.doi.org/10.3390/cells12071016 |
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author | Fabbrizio, Paola Margotta, Cassandra D’Agostino, Jessica Suanno, Giuseppe Quetti, Lorenzo Bendotti, Caterina Nardo, Giovanni |
author_facet | Fabbrizio, Paola Margotta, Cassandra D’Agostino, Jessica Suanno, Giuseppe Quetti, Lorenzo Bendotti, Caterina Nardo, Giovanni |
author_sort | Fabbrizio, Paola |
collection | PubMed |
description | Amyotrophic Lateral Sclerosis (ALS) is the most common adult motor neuron disease, with a poor prognosis, a highly unmet therapeutic need, and a burden on health care costs. Hitherto, strategies aimed at protecting motor neurons have missed or modestly delayed ALS due to a failure in countering the irreversible muscular atrophy. We recently provided direct evidence underlying the pivotal role of macrophages in preserving skeletal muscle mass. Based on these results, we explored whether the modulation of macrophage muscle response and the enhancement of satellite cell differentiation could effectively promote the generation of new myofibers and counteract muscle dysfunction in ALS mice. For this purpose, disease progression and the survival of SOD1G93A mice were evaluated following IL-10 injections in the hindlimb skeletal muscles. Thereafter, we used ex vivo methodologies and in vitro approaches on primary cells to assess the effect of the treatment on the main pathological signatures. We found that IL-10 improved the motor performance of ALS mice by enhancing satellite cells and the muscle pro-regenerative activity of macrophages. This resulted in delayed muscle atrophy and motor neuron loss. Our findings provide the basis for a suitable adjunct multisystem therapeutic approach that pinpoints a primary role of muscle pathology in ALS. |
format | Online Article Text |
id | pubmed-10093513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100935132023-04-13 Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model Fabbrizio, Paola Margotta, Cassandra D’Agostino, Jessica Suanno, Giuseppe Quetti, Lorenzo Bendotti, Caterina Nardo, Giovanni Cells Article Amyotrophic Lateral Sclerosis (ALS) is the most common adult motor neuron disease, with a poor prognosis, a highly unmet therapeutic need, and a burden on health care costs. Hitherto, strategies aimed at protecting motor neurons have missed or modestly delayed ALS due to a failure in countering the irreversible muscular atrophy. We recently provided direct evidence underlying the pivotal role of macrophages in preserving skeletal muscle mass. Based on these results, we explored whether the modulation of macrophage muscle response and the enhancement of satellite cell differentiation could effectively promote the generation of new myofibers and counteract muscle dysfunction in ALS mice. For this purpose, disease progression and the survival of SOD1G93A mice were evaluated following IL-10 injections in the hindlimb skeletal muscles. Thereafter, we used ex vivo methodologies and in vitro approaches on primary cells to assess the effect of the treatment on the main pathological signatures. We found that IL-10 improved the motor performance of ALS mice by enhancing satellite cells and the muscle pro-regenerative activity of macrophages. This resulted in delayed muscle atrophy and motor neuron loss. Our findings provide the basis for a suitable adjunct multisystem therapeutic approach that pinpoints a primary role of muscle pathology in ALS. MDPI 2023-03-26 /pmc/articles/PMC10093513/ /pubmed/37048088 http://dx.doi.org/10.3390/cells12071016 Text en © 2023 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 Fabbrizio, Paola Margotta, Cassandra D’Agostino, Jessica Suanno, Giuseppe Quetti, Lorenzo Bendotti, Caterina Nardo, Giovanni Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model |
title | Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model |
title_full | Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model |
title_fullStr | Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model |
title_full_unstemmed | Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model |
title_short | Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model |
title_sort | intramuscular il-10 administration enhances the activity of myogenic precursor cells and improves motor function in als mouse model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093513/ https://www.ncbi.nlm.nih.gov/pubmed/37048088 http://dx.doi.org/10.3390/cells12071016 |
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