Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight
Abstract 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 sarcopeni...
Main Authors: | , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Nature Portfolio
2023-09-01
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Series: | npj Microgravity |
Online Access: | https://doi.org/10.1038/s41526-023-00322-y |
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author | Maddalena Parafati Shelby Giza Tushar S. Shenoy Jorge A. Mojica-Santiago Meghan Hopf Legrand K. Malany Don Platt Isabel Moore Zachary A. Jacobs Paul Kuehl Jason Rexroat Gentry Barnett Christine E. Schmidt William T. McLamb Twyman Clements Paul M. Coen Siobhan Malany |
author_facet | Maddalena Parafati Shelby Giza Tushar S. Shenoy Jorge A. Mojica-Santiago Meghan Hopf Legrand K. Malany Don Platt Isabel Moore Zachary A. Jacobs Paul Kuehl Jason Rexroat Gentry Barnett Christine E. Schmidt William T. McLamb Twyman Clements Paul M. Coen Siobhan Malany |
author_sort | Maddalena Parafati |
collection | DOAJ |
description | Abstract 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. |
first_indexed | 2024-03-10T17:18:11Z |
format | Article |
id | doaj.art-561fc3bd700b47deb2d2845634e19221 |
institution | Directory Open Access Journal |
issn | 2373-8065 |
language | English |
last_indexed | 2024-03-10T17:18:11Z |
publishDate | 2023-09-01 |
publisher | Nature Portfolio |
record_format | Article |
series | npj Microgravity |
spelling | doaj.art-561fc3bd700b47deb2d2845634e192212023-11-20T10:26:21ZengNature Portfolionpj Microgravity2373-80652023-09-019111110.1038/s41526-023-00322-yHuman skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflightMaddalena Parafati0Shelby Giza1Tushar S. Shenoy2Jorge A. Mojica-Santiago3Meghan Hopf4Legrand K. Malany5Don Platt6Isabel Moore7Zachary A. Jacobs8Paul Kuehl9Jason Rexroat10Gentry Barnett11Christine E. Schmidt12William T. McLamb13Twyman Clements14Paul M. Coen15Siobhan Malany16Department of Pharmacodynamics, College of Pharmacy, University of FloridaDepartment of Pharmacodynamics, College of Pharmacy, University of FloridaDepartment of Pharmacodynamics, College of Pharmacy, University of FloridaJ. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of FloridaTranslational Research Institute, AdventHealthMicro-gRx, INCMicro Aerospace Solutions, INCSpace Tango, LLCSpace Tango, LLCSpace Tango, LLCSpace Tango, LLCSpace Tango, LLCJ. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of FloridaSpace Tango, LLCSpace Tango, LLCTranslational Research Institute, AdventHealthDepartment of Pharmacodynamics, College of Pharmacy, University of FloridaAbstract 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.https://doi.org/10.1038/s41526-023-00322-y |
spellingShingle | Maddalena Parafati Shelby Giza Tushar S. Shenoy Jorge A. Mojica-Santiago Meghan Hopf Legrand K. Malany Don Platt Isabel Moore Zachary A. Jacobs Paul Kuehl Jason Rexroat Gentry Barnett Christine E. Schmidt William T. McLamb Twyman Clements Paul M. Coen Siobhan Malany Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight npj Microgravity |
title | Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight |
title_full | Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight |
title_fullStr | Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight |
title_full_unstemmed | Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight |
title_short | Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight |
title_sort | human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight |
url | https://doi.org/10.1038/s41526-023-00322-y |
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