Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model

被引:4
|
作者
Fabbrizio, Paola [1 ]
Margotta, Cassandra [1 ]
D'Agostino, Jessica [1 ]
Suanno, Giuseppe [1 ]
Quetti, Lorenzo [1 ]
Bendotti, Caterina [1 ]
Nardo, Giovanni [1 ]
机构
[1] Ist Ric Farmacol Mario Negri IRCCS, Dept Neurosci, Lab Mol Neurobiol, Via Mario Negri 2, I-20156 Milan, Italy
关键词
Amyotrophic Lateral Sclerosis; mouse models; skeletal muscle; macrophages; myogenic precursor cells; SKELETAL-MUSCLE REGENERATION; SATELLITE CELLS; STEM-CELLS; INTERLEUKIN-10; MACROPHAGES; DEGENERATION; TRANSITION; EXPRESSION; PHENOTYPE; MONOCYTES;
D O I
10.3390/cells12071016
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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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页数:20
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