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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...

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Autores principales: Fabbrizio, Paola, Margotta, Cassandra, D’Agostino, Jessica, Suanno, Giuseppe, Quetti, Lorenzo, Bendotti, Caterina, Nardo, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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