Effects of Weightlessness on Molecular Changes in Cellular Organisms, Animals and Plants

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 12613

Special Issue Editor


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Guest Editor
1. Department of Microgravity and Translational Regenerative Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
2. Department of Biomedicine, Aarhus University, Aarhus, Denmark
Interests: space medicine; translational regenerative medicine; tissue engineering; cancer research; biomarker
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Space travel has always been a dream of humankind. Deep space exploration will increase the time humans or rodents will spend in microgravity (µg). Moreover, they are exposed to cosmic radiation, hypodynamia, and isolation.

Life in space has enormous well-described effects on health. To counteract these health problems, studies focusing on cardiovascular changes, bone loss, muscle atrophy or the immune system, among others, have been performed in recent years.

This Special Issue (SI) focuses on the impact of real microgravity on humans, animals, microorganisms, and plants during spaceflights. It addresses the impact of cosmic radiation, available countermeasures, and possible applications on Earth.

In addition, studies investigating the effects of simulated microgravity on cells, animals and microorganisms will be published. Ground-based facilities created to provide microgravity on Earth can be used to study molecular biological changes in cells, plants and microorganisms.

Articles and reviews will be published reporting recent advances in gravitational biology, translational regenerative medicine, space medicine and cancer research. Omics investigations and bioinformatics studies will be collected in this Special Issue.

Prof. Dr. Daniela Grimm
Guest Editor

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Keywords

  • cells
  • humans
  • animals
  • plants
  • microorganisms
  • microgravity
  • weightlessness
  • cancer research
  • tissue engineering
  • space-related health problems

Published Papers (7 papers)

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Research

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15 pages, 2370 KiB  
Article
Changes in Gravitaxis and Gene-Expression in an Euglena gracilis Culture over Time
by Julia Krüger, Peter Richter, Julia Stoltze, Binod Prasad, Sebastian M. Strauch, Marcus Krüger, Adeel Nasir and Michael Lebert
Biomolecules 2024, 14(3), 327; https://doi.org/10.3390/biom14030327 - 9 Mar 2024
Viewed by 1237
Abstract
Age-dependent changes in the transcription levels of 5-day-old Euglena gracilis cells, which showed positive gravitaxis, 6-day-old cells without gravitactic orientation, and older cells (9- and 11-day-old, which displayed a precise negative gravitaxis) were determined through microarray analysis. Hierarchical clustering of four independent cell [...] Read more.
Age-dependent changes in the transcription levels of 5-day-old Euglena gracilis cells, which showed positive gravitaxis, 6-day-old cells without gravitactic orientation, and older cells (9- and 11-day-old, which displayed a precise negative gravitaxis) were determined through microarray analysis. Hierarchical clustering of four independent cell cultures revealed pronounced similarities in transcription levels at the same culture age, which proves the reproducibility of the cultivation method. Employing the non-oriented cells from the 6-day-old culture as a reference, about 2779 transcripts were found to be differentially expressed. While positively gravitactic cells (5-day-old culture) showed only minor differences in gene expression compared to the 6-day reference, pronounced changes of mRNAs (mainly an increase) were found in older cells compared to the reference culture. Among others, genes coding for adenylyl cyclases, photosynthesis, and metabolic enzymes were identified to be differentially expressed. The investigated cells were grown in batch cultures, so variations in transcription levels most likely account for factors such as nutrient depletion in the medium and self-shading. Based on these findings, a particular transcript (e.g., transcript 19556) was downregulated using the RNA interference technique. Gravitaxis and phototaxis were impaired in the transformants, indicating the role of this transcript in signal transduction. Results of the experiment are discussed regarding the increasing importance of E. gracilis in biotechnology as a source of valuable products and the possible application of E. gracilis in life-support systems. Full article
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14 pages, 6595 KiB  
Article
Space Flight Enhances Stress Pathways in Human Neural Stem Cells
by Nicholas Carpo, Victoria Tran, Juan Carlos Biancotti, Carlos Cepeda and Araceli Espinosa-Jeffrey
Biomolecules 2024, 14(1), 65; https://doi.org/10.3390/biom14010065 - 3 Jan 2024
Cited by 1 | Viewed by 1310
Abstract
Mammalian cells have evolved to function under Earth’s gravity, but how they respond to microgravity remains largely unknown. Neural stem cells (NSCs) are essential for the maintenance of central nervous system (CNS) functions during development and the regeneration of all CNS cell populations. [...] Read more.
Mammalian cells have evolved to function under Earth’s gravity, but how they respond to microgravity remains largely unknown. Neural stem cells (NSCs) are essential for the maintenance of central nervous system (CNS) functions during development and the regeneration of all CNS cell populations. Here, we examined the behavior of space (SPC)-flown NSCs as they readapted to Earth’s gravity. We found that most of these cells survived the space flight and self-renewed. Yet, some showed enhanced stress responses as well as autophagy-like behavior. To ascertain if the secretome from SPC-flown NSCs contained molecules inducing these responses, we incubated naïve, non-starved NSCs in a medium containing SPC-NSC secretome. We found a four-fold increase in stress responses. Proteomic analysis of the secretome revealed that the protein of the highest content produced by SPC-NSCs was secreted protein acidic and rich in cysteine (SPARC), which induces endoplasmic reticulum (ER) stress, resulting in the cell’s demise. These results offer novel knowledge on the response of neural cells, particularly NSCs, subjected to space microgravity. Moreover, some secreted proteins have been identified as microgravity sensing, paving a new venue for future research aiming at targeting the SPARC metabolism. Although we did not establish a direct relationship between microgravity-induced stress and SPARC as a potential marker, these results represent the first step in the identification of gravity sensing molecules as targets to be modulated and to design effective countermeasures to mitigate intracranial hypertension in astronauts using structure-based protein design. Full article
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24 pages, 4662 KiB  
Article
Structural and Molecular Changes of Human Chondrocytes Exposed to the Rotating Wall Vessel Bioreactor
by Paul Steinwerth, Jessica Bertrand, Viviann Sandt, Shannon Marchal, Jayashree Sahana, Miriam Bollmann, Herbert Schulz, Sascha Kopp, Daniela Grimm and Markus Wehland
Biomolecules 2024, 14(1), 25; https://doi.org/10.3390/biom14010025 - 24 Dec 2023
Viewed by 1290
Abstract
Over the last 30 years, the prevalence of osteoarthritis (OA), a disease characterized by a loss of articular cartilage, has more than doubled worldwide. Patients suffer from pain and progressive loss of joint function. Cartilage is an avascular tissue mostly consisting of extracellular [...] Read more.
Over the last 30 years, the prevalence of osteoarthritis (OA), a disease characterized by a loss of articular cartilage, has more than doubled worldwide. Patients suffer from pain and progressive loss of joint function. Cartilage is an avascular tissue mostly consisting of extracellular matrix with embedded chondrocytes. As such, it does not regenerate naturally, which makes an early onset of OA prevention and treatment a necessity to sustain the patients’ quality of life. In recent years, tissue engineering strategies for the regeneration of cartilage lesions have gained more and more momentum. In this study, we aimed to investigate the scaffold-free 3D cartilage tissue formation under simulated microgravity in the NASA-developed rotating wall vessel (RWV) bioreactor. For this purpose, we cultured both primary human chondrocytes as well as cells from the immortalized line C28/I2 for up to 14 days on the RWV and analyzed tissue morphology, development of apoptosis, and expression of cartilage-specific proteins and genes by histological staining, TUNEL-assays, immunohistochemical detection of collagen species, and quantitative real-time PCR, respectively. We observed spheroid formation in both cell types starting on day 3. After 14 days, constructs from C28/I2 cells had diameters of up to 5 mm, while primary chondrocyte spheroids were slightly smaller with 3 mm. Further inspection of the 14-day-old C28/I2 spheroids revealed a characteristic cartilage morphology with collagen-type 1, -type 2, and -type 10 positivity. Interestingly, these tissues were less susceptible to RWV-induced differential gene expression than those formed from primary chondrocytes, which showed significant changes in the regulation of IL6, ACTB, TUBB, VIM, COL1A1, COL10A1, MMP1, MMP3, MMP13, ITGB1, LAMA1, RUNX3, SOX9, and CASP3 gene expression. These diverging findings might reflect the differences between primary and immortalized cells. Taken together, this study shows that simulated microgravity using the RWV bioreactor is suitable to engineer dense 3D cartilage-like tissue without addition of scaffolds or any other artificial materials. Both primary articular cells and the stable chondrocyte cell line C28/I2 formed 3D neocartilage when exposed for 14 days to an RWV. Full article
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17 pages, 5379 KiB  
Article
Transcriptomic Effects on the Mouse Heart Following 30 Days on the International Space Station
by Alicia L. Veliz, Lana Mamoun, Lorelei Hughes, Richard Vega, Bailey Holmes, Andrea Monteon, Jillian Bray, Michael J. Pecaut and Mary Kearns-Jonker
Biomolecules 2023, 13(2), 371; https://doi.org/10.3390/biom13020371 - 15 Feb 2023
Cited by 3 | Viewed by 2671
Abstract
Efforts to understand the impact of spaceflight on the human body stem from growing interest in long-term space travel. Multiple organ systems are affected by microgravity and radiation, including the cardiovascular system. Previous transcriptomic studies have sought to reveal the changes in gene [...] Read more.
Efforts to understand the impact of spaceflight on the human body stem from growing interest in long-term space travel. Multiple organ systems are affected by microgravity and radiation, including the cardiovascular system. Previous transcriptomic studies have sought to reveal the changes in gene expression after spaceflight. However, little is known about the impact of long-term spaceflight on the mouse heart in vivo. This study focuses on the transcriptomic changes in the hearts of female C57BL/6J mice flown on the International Space Station (ISS) for 30 days. RNA was isolated from the hearts of three flight and three comparable ground control mice and RNA sequencing was performed. Our analyses showed that 1147 transcripts were significantly regulated after spaceflight. The MAPK, PI3K-Akt, and GPCR signaling pathways were predicted to be activated. Transcripts related to cytoskeleton breakdown and organization were upregulated, but no significant change in the expression of extracellular matrix (ECM) components or oxidative stress pathway-associated transcripts occurred. Our results indicate an absence of cellular senescence, and a significant upregulation of transcripts associated with the cell cycle. Transcripts related to cellular maintenance and survival were most affected by spaceflight, suggesting that cardiovascular transcriptome initiates an adaptive response to long-term spaceflight. Full article
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14 pages, 5510 KiB  
Article
Oligodendrocyte Progenitors Display Enhanced Proliferation and Autophagy after Space Flight
by Victoria Tran, Nicholas Carpo, Carlos Cepeda and Araceli Espinosa-Jeffrey
Biomolecules 2023, 13(2), 201; https://doi.org/10.3390/biom13020201 - 19 Jan 2023
Cited by 3 | Viewed by 2010
Abstract
Intracranial hypertension (ICP) and visual impairment intracranial pressure (VIIP) are some of the consequences of long-term space missions. Here we examined the behavior of oligodendrocyte progenitors (OLPs) after space flight using time-lapse microscopy. We show that most OLPs divided more than ground control [...] Read more.
Intracranial hypertension (ICP) and visual impairment intracranial pressure (VIIP) are some of the consequences of long-term space missions. Here we examined the behavior of oligodendrocyte progenitors (OLPs) after space flight using time-lapse microscopy. We show that most OLPs divided more than ground control (GC) counterparts did. Nonetheless, a subpopulation of OLPs flown to space presented a significant increase in autophagic cell death. Examination of the proteomic profile of the secretome of space flown OLPs (SPC-OLPs) revealed that the stress protein heat shock protein-90 beta “HSP-90β” was the 5th most enriched (6.8 times) and the secreted protein acidic and rich in cysteine “SPARC” was the 7th most enriched (5.2 times), with respect to ground control cells. SPARC induces endoplasmic reticulum stress, which leads to autophagy. Given the roles and importance of these two proteins in mammalian cells’ metabolism, their upregulation may hold the key to modulating cell proliferation and autophagy, in order to mitigate ICP and VIIP during and after space missions. Full article
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22 pages, 6617 KiB  
Article
Effects of High Glucose on Human Endothelial Cells Exposed to Simulated Microgravity
by Justina Jokšienė, Jayashree Sahana, Markus Wehland, Herbert Schulz, José Luis Cortés-Sánchez, Judit Prat-Duran, Daniela Grimm and Ulf Simonsen
Biomolecules 2023, 13(2), 189; https://doi.org/10.3390/biom13020189 - 17 Jan 2023
Cited by 3 | Viewed by 2297
Abstract
A diabetogenic state induced by spaceflight provokes stress and health problems in astronauts. Microgravity (µg) is one of the main stressors in space causing hyperglycaemia. However, the underlying molecular pathways and synergistic effects of µg and hyperglycaemia are not fully [...] Read more.
A diabetogenic state induced by spaceflight provokes stress and health problems in astronauts. Microgravity (µg) is one of the main stressors in space causing hyperglycaemia. However, the underlying molecular pathways and synergistic effects of µg and hyperglycaemia are not fully understood. In this study, we investigated the effects of high glucose on EA.hy926 endothelial cells in simulated µg (s-µg) using a 3D clinostat and static normogravity (1g) conditions. After 14 days of cell culture under s-µg and 1g conditions, we compared the expression of extracellular matrix (ECM), inflammation, glucose metabolism, and apoptosis-related genes and proteins through qPCR, immunofluorescence, and Western blot analyses, respectively. Apoptosis was evaluated via TUNEL staining. Gene interactions were examined via STRING analysis. Our results show that glucose concentrations had a weaker effect than altered gravity. µg downregulated the ECM gene and protein expression and had a stronger influence on glucose metabolism than hyperglycaemia. Moreover, hyperglycaemia caused more pronounced changes in 3D cultures than in 2D cultures, including bigger and a greater number of spheroids, upregulation of NOX4 and the apoptotic proteins NF-κB and CASP3, and downregulation of fibronectin and transglutaminase-2. Our findings bring new insights into the possible molecular pathways involved in the diabetogenic vascular effects in µg. Full article
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Review

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15 pages, 1628 KiB  
Review
Cellular and Molecular Effects of Microgravity on the Immune System: A Focus on Bioactive Lipids
by Marina Fava, Noemi De Dominicis, Giulia Forte, Monica Bari, Alessandro Leuti and Mauro Maccarrone
Biomolecules 2024, 14(4), 446; https://doi.org/10.3390/biom14040446 - 5 Apr 2024
Viewed by 904
Abstract
Microgravity is one of the main stressors that astronauts are exposed to during space missions. This condition has been linked to many disorders, including those that feature dysfunctional immune homeostasis and inflammatory damage. Over the past 30 years, a significant body of work [...] Read more.
Microgravity is one of the main stressors that astronauts are exposed to during space missions. This condition has been linked to many disorders, including those that feature dysfunctional immune homeostasis and inflammatory damage. Over the past 30 years, a significant body of work has been gathered connecting weightlessness—either authentic or simulated—to an inefficient reaction to pathogens, dysfunctional production of cytokines and impaired survival of immune cells. These processes are also orchestrated by a plethora of bioactive lipids, produced by virtually all cells involved in immune events, which control the induction, magnitude, outcome, compartmentalization and trafficking of immunocytes during the response to injury. Despite their crucial importance in inflammation and its modulation, however, data concerning the role of bioactive lipids in microgravity-induced immune dysfunctions are surprisingly scarce, both in quantity and in variety, and the vast majority of it focuses on two lipid classes, namely eicosanoids and endocannabinoids. The present review aims to outline the accumulated knowledge addressing the effects elicited by microgravity—both simulated and authentic—on the metabolism and signaling of these two prominent lipid groups in the context of immune and inflammatory homeostasis. Full article
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