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Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight
npj Microgravity ( IF 5.1 ) Pub Date : 2023-09-15 , DOI: 10.1038/s41526-023-00322-y
Maddalena Parafati 1 , Shelby Giza 1 , Tushar S Shenoy 1 , Jorge A Mojica-Santiago 2 , Meghan Hopf 3 , Legrand K Malany 4 , Don Platt 5 , Isabel Moore 6 , Zachary A Jacobs 6 , Paul Kuehl 6 , Jason Rexroat 6 , Gentry Barnett 6 , Christine E Schmidt 2 , William T McLamb 6 , Twyman Clements 6 , Paul M Coen 3 , Siobhan Malany 1
Affiliation  

Microphysiological systems provide the opportunity to model accelerated changes at the human tissue level in the extreme space environment. Spaceflight-induced muscle atrophy experienced by astronauts shares similar physiological changes to muscle wasting in older adults, known as sarcopenia. These shared attributes provide a rationale for investigating molecular changes in muscle cells exposed to spaceflight that may mimic the underlying pathophysiology of sarcopenia. We report the results from three-dimensional myobundles derived from muscle biopsies from young and older adults, integrated into an autonomous CubeLab™, and flown to the International Space Station (ISS) aboard SpaceX CRS-21 as part of the NIH/NASA funded Tissue Chips in Space program. Global transcriptomic RNA-Seq analyses comparing the myobundles in space and on the ground revealed downregulation of shared transcripts related to myoblast proliferation and muscle differentiation. The analyses also revealed downregulated differentially expressed gene pathways related to muscle metabolism unique to myobundles derived from the older cohort exposed to the space environment compared to ground controls. Gene classes related to inflammatory pathways were downregulated in flight samples cultured from the younger cohort compared to ground controls. Our muscle tissue chip platform provides an approach to studying the cell autonomous effects of spaceflight on muscle cell biology that may not be appreciated on the whole organ or organism level and sets the stage for continued data collection from muscle tissue chip experimentation in microgravity. We also report on the challenges and opportunities for conducting autonomous tissue-on-chip CubeLabTM payloads on the ISS.



中文翻译:

人体骨骼肌组织芯片自主有效载​​荷揭示了太空飞行导致的纤维类型和代谢基因表达的变化

微生理系统提供了模拟极端太空环境中人体组织水平加速变化的机会。宇航员经历的太空飞行引起的肌肉萎缩与老年人的肌肉萎缩有相似的生理变化,即肌肉减少症。这些共同的属性为研究暴露于太空飞行的肌肉细胞的分子变化提供了理论依据,这些变化可能模拟肌肉减少症的潜在病理生理学。我们报告了从年轻人和老年人的肌肉活检中提取的三维肌束的结果,这些肌束集成到自主的 CubeLab™ 中,并作为 NIH/NASA 资助的组织的一部分搭乘 SpaceX CRS-21 飞往国际空间站 (ISS)太空芯片计划。比较太空和地面肌束的全局转录组 RNA-Seq 分析揭示了与成肌细胞增殖和肌肉分化相关的共享转录本的下调。分析还揭示了与地面对照相比,暴露于太空环境的老年群体的肌束特有的与肌肉代谢相关的差异表达基因通路的下调。与地面对照相比,年轻队列培养的飞行样本中与炎症途径相关的基因类别下调。我们的肌肉组织芯片平台提供了一种研究航天对肌肉细胞生物学的细胞自主影响的方法,这种影响在整个器官或生物体水平上可能无法被理解,并为微重力下肌肉组织芯片实验的持续数据收集奠定了基础。我们还报告了在国际空间站上进行自主芯片组织 CubeLab TM有效载荷的挑战和机遇。

更新日期:2023-09-16
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