{"title":"Mesenchymal stem cell transplant as an intervention to ameliorate disuse-induced muscle atrophy in a mouse model of simulated microgravity","authors":"","doi":"10.1016/j.actaastro.2024.10.060","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>The hindlimb unloaded (HU) mouse model exhibits disuse-induced muscle atrophy. However, effective interventions remain elusive. We investigated the therapeutic potential of mesenchymal stem cells (MSC) transplant on muscle decline in HU mice.</div></div><div><h3>Methods</h3><div>We divided 4-month-old male c57BL/6j mice into controls and HU mice treated with PBS as placebo (HU-PBS) or MSCs (HU-MSC; one million cells/100 μl PBS into gastrocnemius muscles once a week) for three weeks. We measured muscle mass, grip strength, and an unbiased transcriptome analysis of gastrocnemius muscles.</div></div><div><h3>Results</h3><div>MSC treatment prevented muscle atrophy and improved grip strength in HU mice. Transcriptome analysis revealed MSC-induced unique (557 genes) and differential (1214 genes) expressions of several genes compared to the HU-PBS group. GO and KEGG term analysis revealed an HU-induced downregulation of pathways associated with the regulation of contractile apparatus, neuromuscular junction, and satellite cell function, which were partly reversed with MSC treatment. Lastly, MSC treatment also upregulated the pathways controlling muscle differentiation and growth in the HU mice.</div></div><div><h3>Conclusion</h3><div>Altogether, we report the therapeutic potential of MSCs in treating disuse-induced muscle atrophy and weakness. Our study may help unravel novel molecular mechanisms involved in MSCs-induced muscle restoration.</div></div>","PeriodicalId":44971,"journal":{"name":"Acta Astronautica","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Astronautica","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0094576524006349","RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, AEROSPACE","Score":null,"Total":0}
引用次数: 0
Abstract
Background
The hindlimb unloaded (HU) mouse model exhibits disuse-induced muscle atrophy. However, effective interventions remain elusive. We investigated the therapeutic potential of mesenchymal stem cells (MSC) transplant on muscle decline in HU mice.
Methods
We divided 4-month-old male c57BL/6j mice into controls and HU mice treated with PBS as placebo (HU-PBS) or MSCs (HU-MSC; one million cells/100 μl PBS into gastrocnemius muscles once a week) for three weeks. We measured muscle mass, grip strength, and an unbiased transcriptome analysis of gastrocnemius muscles.
Results
MSC treatment prevented muscle atrophy and improved grip strength in HU mice. Transcriptome analysis revealed MSC-induced unique (557 genes) and differential (1214 genes) expressions of several genes compared to the HU-PBS group. GO and KEGG term analysis revealed an HU-induced downregulation of pathways associated with the regulation of contractile apparatus, neuromuscular junction, and satellite cell function, which were partly reversed with MSC treatment. Lastly, MSC treatment also upregulated the pathways controlling muscle differentiation and growth in the HU mice.
Conclusion
Altogether, we report the therapeutic potential of MSCs in treating disuse-induced muscle atrophy and weakness. Our study may help unravel novel molecular mechanisms involved in MSCs-induced muscle restoration.
期刊介绍:
Acta Astronautica is sponsored by the International Academy of Astronautics. Content is based on original contributions in all fields of basic, engineering, life and social space sciences and of space technology related to:
The peaceful scientific exploration of space,
Its exploitation for human welfare and progress,
Conception, design, development and operation of space-borne and Earth-based systems,
In addition to regular issues, the journal publishes selected proceedings of the annual International Astronautical Congress (IAC), transactions of the IAA and special issues on topics of current interest, such as microgravity, space station technology, geostationary orbits, and space economics. Other subject areas include satellite technology, space transportation and communications, space energy, power and propulsion, astrodynamics, extraterrestrial intelligence and Earth observations.