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Microgravity, Cell Shape and Gene Expression: State of the Art, Challenges and Prospects

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Dr. Masahiro Terada

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Unit of Synergetic Studies for Space, Kyoto University, Kyoto 606-8501, Japan
Interests: space medicine; space life sciences; physiology; cell biology; pharmacology; exercise; countermeasure; artificial gravity; space education
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Dear Colleagues,

It is anticipated that more humans will spend time in space in the future, and that the duration of stay will become longer. For this reason, the field of space medicine, which studies how the space environment affects the human body in the long term, is becoming even more important.

This Special Issue focuses on research on the effects of the space environment on living organisms. Space medical research includes not only space experiments but also analog experiments that simulate the space environment. Therefore, this Special Issue covers a wide range of research examining physiological mechanisms and gene expression in organisms and living beings both during space stays and through ground-based research. We welcome you to submit research on these topics.

Dr. Masahiro Terada
Guest Editor

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36 pages, 6557 KB

Open AccessReview

New Knowledge About Tissue Engineering Under Microgravity Conditions in Space and on Earth

by Markus Wehland, Thomas J. Corydon, Luis Fernando González-Torres, Fatima Abdelfattah, Jayashree Sahana, Herbert Schulz, Ashwini Mushunuri, Hanna Burenkova, Simon L. Wuest, Marcus Krüger, Armin Kraus and Daniela Grimm

Int. J. Mol. Sci. 2026, 27(1), 341; https://doi.org/10.3390/ijms27010341 - 28 Dec 2025

Viewed by 1554

Abstract

Microgravity (µg)-generated three-dimensional (3D) multicellular aggregates can serve as models of tissue and disease development. They are relevant in the fields of cancer and in vitro metastasis or regenerative medicine (tissue engineering). Driven by the 3R concept—replacement, reduction, and refinement of animal testing—µg-exposure of human cells represents a new alternative method that avoids animal experiments entirely. New Approach Methodologies (NAMs) are used in biomedical research, pharmacology, toxicology, cancer research, radiotherapy, and translational regenerative medicine. Various types of human cells grow as 3D spheroids or organoids when exposed to µg-conditions provided by µg simulating instruments on Earth. Examples for such µg-simulators are the Rotating Wall Vessel, the Random Positioning Machine, and the 2D or 3D clinostat. This review summarizes the most recent literature focusing on µg-engineered tissues. We are discussing all reports examining different tumor cell types from breast, lung, thyroid, prostate, and gastrointestinal cancers. Moreover, we are focusing on µg-generated spheroids and organoids derived from healthy cells like chondrocytes, stem cells, bone cells, endothelial cells, and cardiovascular cells. The obtained data from NAMs and µg-experiments clearly imply that they can support translational medicine on Earth. Full article

(This article belongs to the Special Issue Microgravity, Cell Shape and Gene Expression: State of the Art, Challenges and Prospects)

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19 pages, 4950 KB

Open AccessArticle

Mechanisms of Mechanical Stress-Induced Vascular Remodeling via the Lactate-PKM2 Axis and Implications for Microgravity Adaptation

by Na Li, Ling Liu, Dong Wang, Jing Wang, Yateng Tie, Xi Li, Jiaxiang Li, Yuan Gao, Changbin Yang and Yongchun Wang

Int. J. Mol. Sci. 2026, 27(7), 3298; https://doi.org/10.3390/ijms27073298 - 5 Apr 2026

Viewed by 356

Abstract

Vascular remodeling driven by the phenotypic switching of vascular smooth muscle cells (VSMCs) poses a significant health risk to astronauts during long-duration spaceflight. While the morphological and molecular changes are well recognized, the underlying metabolic drivers and potential translational countermeasures remain elusive. To investigate the metabolic determinants of VSMCs phenotypic switching, human aortic smooth muscle cells (HASMCs) were subjected to cyclic mechanical stretch, an in vitro model offering indirect mechanistic insights into mechanical loading conditions relevant to spaceflight-associated hemodynamic alterations. An integrated approach combining quantitative proteomics, flux analysis (Seahorse), and functional assays (cell cycle, wound healing, transwell) was used to characterize the accompanying metabolic and phenotypic alterations. Molecular mechanisms were assessed using immunoprecipitation, protein crosslinking, and immunofluorescence. Mechanical stretch triggered a contractile-to-synthetic phenotypic switch in HASMCs, accompanied by a shift from oxidative phosphorylation to aerobic glycolysis. Pyruvate kinase M2 (PKM2) was identified as a central metabolic regulator of this process, its silencing reversed the pro-synthetic phenotype. Notably, lactate, a glycolytic product, was found to exert a self-limiting feedback signal. Exogenous lactate suppressed the synthetic switch in associated with increased PKM2 lactylation. Further analysis indicated that PKM2 lactylation was associated with enhanced stability of its active tetrameric conformation, which was associated with a metabolic shift toward oxidative phosphorylation and restored expression of contractile markers. Although specific lactylation sites on PKM2 were not identified in this study, and direct causality between lactylation and tetramerization remains to be established, these findings identify a previously unrecognized association. This study reveals a novel metabolic regulatory mechanism in which lactate correlates with the suppression of synthetic switching of VSMCs, linked to PKM2 lactylation and tetramer stabilization. The observed lactate-PKM2 axis represents a candidate metabolic node associated with VSMCs phenotype regulation and offers a potential therapeutic target for modulating vascular remodeling. Upon direct validation under relevant conditions in future studies, this mechanism may inform the development of novel therapeutic strategies for managing vascular adaptation during long-duration spaceflight and other aerospace-related physiological challenges. Full article

(This article belongs to the Special Issue Microgravity, Cell Shape and Gene Expression: State of the Art, Challenges and Prospects)

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