International Journal of Molecular Sciences

Editorial

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7 pages, 224 KiB

Open AccessEditorial

Microgravity and Space Medicine

by Daniela Grimm

Int. J. Mol. Sci. 2021, 22(13), 6697; https://doi.org/10.3390/ijms22136697 - 22 Jun 2021

Cited by 11 | Viewed by 4833

Abstract

This Special Issue (SI), “Microgravity and Space Medicine”, covers research articles and reviews focusing on gravitational biology, cancer research and space medicine [...] Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

Research

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18 pages, 4531 KiB

Open AccessArticle

The Impact of Spaceflight and Microgravity on the Human Islet-1+ Cardiovascular Progenitor Cell Transcriptome

by Victor Camberos, Jonathan Baio, Ana Mandujano, Aida F. Martinez, Leonard Bailey, Nahidh Hasaniya and Mary Kearns-Jonker

Int. J. Mol. Sci. 2021, 22(7), 3577; https://doi.org/10.3390/ijms22073577 - 30 Mar 2021

Cited by 18 | Viewed by 5080

Abstract

Understanding the transcriptomic impact of microgravity and the spaceflight environment is relevant for future missions in space and microgravity-based applications designed to benefit life on Earth. Here, we investigated the transcriptome of adult and neonatal cardiovascular progenitors following culture aboard the International Space [...] Read more.

Understanding the transcriptomic impact of microgravity and the spaceflight environment is relevant for future missions in space and microgravity-based applications designed to benefit life on Earth. Here, we investigated the transcriptome of adult and neonatal cardiovascular progenitors following culture aboard the International Space Station for 30 days and compared it to the transcriptome of clonally identical cells cultured on Earth. Cardiovascular progenitors acquire a gene expression profile representative of an early-stage, dedifferentiated, stem-like state, regardless of age. Signaling pathways that support cell proliferation and survival were induced by spaceflight along with transcripts related to cell cycle re-entry, cardiovascular development, and oxidative stress. These findings contribute new insight into the multifaceted influence of reduced gravitational environments. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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14 pages, 27985 KiB

Open AccessArticle

Nox2 Inhibition Regulates Stress Response and Mitigates Skeletal Muscle Fiber Atrophy during Simulated Microgravity

by John M. Lawler, Jeffrey M. Hord, Pat Ryan, Dylan Holly, Mariana Janini Gomes, Dinah Rodriguez, Vinicius Guzzoni, Erika Garcia-Villatoro, Chase Green, Yang Lee, Sarah Little, Marcela Garcia, Lorrie Hill, Mary-Catherine Brooks, Matthew S. Lawler, Nicolette Keys, Amin Mohajeri and Khaled Y. Kamal

Int. J. Mol. Sci. 2021, 22(6), 3252; https://doi.org/10.3390/ijms22063252 - 23 Mar 2021

Cited by 13 | Viewed by 4542

Abstract

Insufficient stress response and elevated oxidative stress can contribute to skeletal muscle atrophy during mechanical unloading (e.g., spaceflight and bedrest). Perturbations in heat shock proteins (e.g., HSP70), antioxidant enzymes, and sarcolemmal neuronal nitric oxidase synthase (nNOS) have been linked to unloading-induced atrophy. We [...] Read more.

Insufficient stress response and elevated oxidative stress can contribute to skeletal muscle atrophy during mechanical unloading (e.g., spaceflight and bedrest). Perturbations in heat shock proteins (e.g., HSP70), antioxidant enzymes, and sarcolemmal neuronal nitric oxidase synthase (nNOS) have been linked to unloading-induced atrophy. We recently discovered that the sarcolemmal NADPH oxidase-2 complex (Nox2) is elevated during unloading, downstream of angiotensin II receptor 1, and concomitant with atrophy. Here, we hypothesized that peptidyl inhibition of Nox2 would attenuate disruption of HSP70, MnSOD, and sarcolemmal nNOS during unloading, and thus muscle fiber atrophy. F344 rats were divided into control (CON), hindlimb unloaded (HU), and hindlimb unloaded +7.5 mg/kg/day gp91ds-tat (HUG) groups. Unloading-induced elevation of the Nox2 subunit p67phox-positive staining was mitigated by gp91ds-tat. HSP70 protein abundance was significantly lower in HU muscles, but not HUG. MnSOD decreased with unloading; however, MnSOD was not rescued by gp91ds-tat. In contrast, Nox2 inhibition protected against unloading suppression of the antioxidant transcription factor Nrf2. nNOS bioactivity was reduced by HU, an effect abrogated by Nox2 inhibition. Unloading-induced soleus fiber atrophy was significantly attenuated by gp91ds-tat. These data establish a causal role for Nox2 in unloading-induced muscle atrophy, linked to preservation of HSP70, Nrf2, and sarcolemmal nNOS. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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19 pages, 3543 KiB

Open AccessArticle

Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space

by Petra M. Wise, Paolo Neviani, Stefan Riwaldt, Thomas Juhl Corydon, Markus Wehland, Markus Braun, Marcus Krüger, Manfred Infanger and Daniela Grimm

Int. J. Mol. Sci. 2021, 22(4), 2132; https://doi.org/10.3390/ijms22042132 - 21 Feb 2021

Cited by 14 | Viewed by 3983

Abstract

Space travel has always been the man’s ultimate destination. With the ability of spaceflight though, came the realization that exposure to microgravity has lasting effects on the human body. To counteract these, many studies were and are undertaken, on multiple levels. Changes in [...] Read more.

Space travel has always been the man’s ultimate destination. With the ability of spaceflight though, came the realization that exposure to microgravity has lasting effects on the human body. To counteract these, many studies were and are undertaken, on multiple levels. Changes in cell growth, gene, and protein expression have been described in different models on Earth and in space. Extracellular vesicles, and in particular exosomes, are important cell-cell communicators, being secreted from almost all the cells and therefore, are a perfect target to further investigate the underlying reasons of the organism’s adaptations to microgravity. Here, we studied supernatants harvested from the CellBox-1 experiment, which featured human thyroid cancer cells flown to the International Space Station during the SpaceX CRS-3 cargo mission. The initial results show differences in the number of secreted exosomes, as well as in the distribution of subpopulations in regards to their surface protein expression. Notably, alteration of their population regarding the tetraspanin surface expression was observed. This is a promising step into a new area of microgravity research and will potentially lead to the discovery of new biomarkers and pathways of cellular cross-talk. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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26 pages, 12337 KiB

Open AccessArticle

Survival Pathways Are Differently Affected by Microgravity in Normal and Cancerous Breast Cells

by Noemi Monti, Maria Grazia Masiello, Sara Proietti, Angela Catizone, Giulia Ricci, Abdel Halim Harrath, Saleh H. Alwasel, Alessandra Cucina and Mariano Bizzarri

Int. J. Mol. Sci. 2021, 22(2), 862; https://doi.org/10.3390/ijms22020862 - 16 Jan 2021

Cited by 21 | Viewed by 2972

Abstract

Metazoan living cells exposed to microgravity undergo dramatic changes in morphological and biological properties, which ultimately lead to apoptosis and phenotype reprogramming. However, apoptosis can occur at very different rates depending on the experimental model, and in some cases, cells seem to be [...] Read more.

Metazoan living cells exposed to microgravity undergo dramatic changes in morphological and biological properties, which ultimately lead to apoptosis and phenotype reprogramming. However, apoptosis can occur at very different rates depending on the experimental model, and in some cases, cells seem to be paradoxically protected from programmed cell death during weightlessness. These controversial results can be explained by considering the notion that the behavior of adherent cells dramatically diverges in respect to that of detached cells, organized into organoids-like, floating structures. We investigated both normal (MCF10A) and cancerous (MCF-7) breast cells and found that appreciable apoptosis occurs only after 72 h in MCF-7 cells growing in organoid-like structures, in which major modifications of cytoskeleton components were observed. Indeed, preserving cell attachment to the substrate allows cells to upregulate distinct Akt- and ERK-dependent pathways in MCF-7 and MCF-10A cells, respectively. These findings show that survival strategies may differ between cell types but cannot provide sufficient protection against weightlessness-induced apoptosis alone if adhesion to the substrate is perturbed. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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24 pages, 8083 KiB

Open AccessArticle

Tissue Engineering of Cartilage Using a Random Positioning Machine

by Markus Wehland, Paul Steinwerth, Ganna Aleshcheva, Jayashree Sahana, Ruth Hemmersbach, Ronald Lützenberg, Sascha Kopp, Manfred Infanger and Daniela Grimm

Int. J. Mol. Sci. 2020, 21(24), 9596; https://doi.org/10.3390/ijms21249596 - 16 Dec 2020

Cited by 26 | Viewed by 4452

Abstract

Articular cartilage is a skeletal tissue of avascular nature and limited self-repair capacity. Cartilage-degenerative diseases, such as osteoarthritis (OA), are difficult to treat and often necessitate joint replacement surgery. Cartilage is a tough but flexible material and relatively easy to damage. It is, [...] Read more.

Articular cartilage is a skeletal tissue of avascular nature and limited self-repair capacity. Cartilage-degenerative diseases, such as osteoarthritis (OA), are difficult to treat and often necessitate joint replacement surgery. Cartilage is a tough but flexible material and relatively easy to damage. It is, therefore, of high interest to develop methods allowing chondrocytes to recolonize, to rebuild the cartilage and to restore joint functionality. Here we studied the in vitro production of cartilage-like tissue using human articular chondrocytes exposed to the Random Positioning Machine (RPM), a device to simulate certain aspects of microgravity on Earth. To screen early adoption reactions of chondrocytes exposed to the RPM, we performed quantitative real-time PCR analyses after 24 h on chondrocytes cultured in DMEM/F-12. A significant up-regulation in the gene expression of IL6, RUNX2, RUNX3, SPP1, SOX6, SOX9, and MMP13 was detected, while the levels of IL8, ACAN, PRG4, ITGB1, TGFB1, COL1A1, COL2A1, COL10A1, SOD3, SOX5, MMP1, and MMP2 mRNAs remained unchanged. The STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) analysis demonstrated among others the importance of these differentially regulated genes for cartilage formation. Chondrocytes grown in DMEM/F-12 medium produced three-dimensional (3D) spheroids after five days without the addition of scaffolds. On day 28, the produced tissue constructs reached up to 2 mm in diameter. Using specific chondrocyte growth medium, similar results were achieved within 14 days. Spheroids from both types of culture media showed the typical cartilage morphology with aggrecan positivity. Intermediate filaments form clusters under RPM conditions as detected by vimentin staining after 7 d and 14 d. Larger meshes appear in the network in 28-day samples. Furthermore, they were able to form a confluent chondrocyte monolayer after being transferred back into cell culture flasks in 1 g conditions showing their suitability for transplantation into joints. Our results demonstrate that the cultivation medium has a direct influence on the velocity of tissue formation and tissue composition. The spheroids show properties that make them interesting candidates for cellular cartilage regeneration approaches in trauma and OA therapy. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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17 pages, 2378 KiB

Open AccessArticle

Integrative Analysis of Regulatory Module Reveals Associations of Microgravity with Dysfunctions of Multi-body Systems and Tumorigenesis

by Mengqin Yuan, Haizhou Liu, Shunheng Zhou, Xu Zhou, Yu-e Huang, Fei Hou and Wei Jiang

Int. J. Mol. Sci. 2020, 21(20), 7585; https://doi.org/10.3390/ijms21207585 - 14 Oct 2020

Cited by 5 | Viewed by 2435

Abstract

Previous studies have demonstrated that microgravity could lead to health risks. The investigation of the molecular mechanisms from the aspect of systems biology has not been performed yet. Here, we integratively analyzed transcriptional and post-transcriptional regulations based on gene and miRNA expression profiles [...] Read more.

Previous studies have demonstrated that microgravity could lead to health risks. The investigation of the molecular mechanisms from the aspect of systems biology has not been performed yet. Here, we integratively analyzed transcriptional and post-transcriptional regulations based on gene and miRNA expression profiles in human peripheral blood lymphocytes cultured in modeled microgravity. Two hundred and thirty dysregulated TF-miRNA (transcription factor and microRNA) feed-forward loops (FFLs) were identified in microgravity. The immune, cardiovascular, endocrine, nervous and skeletal system subnetworks were constructed according to the functions of dysregulated FFLs. Taking the skeletal system as an example, most of genes and miRNAs in the subnetwork were involved in bone loss. In addition, several drugs have been predicted to have potential to reduce bone loss, such as traditional Chinese medicines Emodin and Ginsenoside Rh2. Furthermore, we investigated the relationships between microgravity and 20 cancer types, and found that most of cancers might be promoted by microgravity. For example, rectum adenocarcinoma (READ) might be induced by microgravity through reducing antigen presentation and suppressing IgA-antibody-secreting cells’ migration. Collectively, TF-miRNA FFL might provide a novel mechanism to elucidate the changes induced by microgravity, serve as drug targets to relieve microgravity effects, and give new insights to explore the relationships between microgravity and cancers. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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17 pages, 2742 KiB

Open AccessArticle

Changes in Nuclear Shape and Gene Expression in Response to Simulated Microgravity Are LINC Complex-Dependent

by Srujana Neelam, Brian Richardson, Richard Barker, Ceasar Udave, Simon Gilroy, Mark J. Cameron, Howard G. Levine and Ye Zhang

Int. J. Mol. Sci. 2020, 21(18), 6762; https://doi.org/10.3390/ijms21186762 - 15 Sep 2020

Cited by 18 | Viewed by 4578

Abstract

Microgravity is known to affect the organization of the cytoskeleton, cell and nuclear morphology and to elicit differential expression of genes associated with the cytoskeleton, focal adhesions and the extracellular matrix. Although the nucleus is mechanically connected to the cytoskeleton through the Linker [...] Read more.

Microgravity is known to affect the organization of the cytoskeleton, cell and nuclear morphology and to elicit differential expression of genes associated with the cytoskeleton, focal adhesions and the extracellular matrix. Although the nucleus is mechanically connected to the cytoskeleton through the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, the role of this group of proteins in these responses to microgravity has yet to be defined. In our study, we used a simulated microgravity device, a 3-D clinostat (Gravite), to investigate whether the LINC complex mediates cellular responses to the simulated microgravity environment. We show that nuclear shape and differential gene expression are both responsive to simulated microgravity in a LINC-dependent manner and that this response changes with the duration of exposure to simulated microgravity. These LINC-dependent genes likely represent elements normally regulated by the mechanical forces imposed by gravity on Earth. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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14 pages, 1702 KiB

Open AccessArticle

Drosophila melanogaster Sperm under Simulated Microgravity and a Hypomagnetic Field: Motility and Cell Respiration

by Irina V. Ogneva, Maria A. Usik, Maria V. Burtseva, Nikolay S. Biryukov, Yuliya S. Zhdankina, Vladimir N. Sychev and Oleg I. Orlov

Int. J. Mol. Sci. 2020, 21(17), 5985; https://doi.org/10.3390/ijms21175985 - 20 Aug 2020

Cited by 21 | Viewed by 3240

Abstract

The role of the Earth’s gravitational and magnetic fields in the evolution and maintenance of normal processes of various animal species remains unclear. The aim of this work was to determine the effect of simulated microgravity and hypomagnetic conditions for 1, 3, and [...] Read more.

The role of the Earth’s gravitational and magnetic fields in the evolution and maintenance of normal processes of various animal species remains unclear. The aim of this work was to determine the effect of simulated microgravity and hypomagnetic conditions for 1, 3, and 6 h on the sperm motility of the fruit fly Drosophila melanogaster. In addition to the usual diet, the groups were administered oral essential phospholipids at a dosage of 500 mg/kg in medium. The speed of the sperm tails was determined by video recording and analysis of the obtained video files, protein content by western blotting, and cell respiration by polarography. The results indicated an increase in the speed of movement of the sperm tails after 6 h in simulated microgravity. The levels of proteins that form the axoneme of the sperm tail did not change, but cellular respiration was altered. A similar effect occurred with the administration of essential phospholipids. These results may be due to a change in the level of phosphorylation of motor proteins. Exposure to hypomagnetic conditions led to a decrease in motility after 6 h against a background of a decrease in the rate of cellular respiration due to complex I of the respiratory chain. This effect was not observed in the flies that received essential phospholipids. However, after 1 h under hypomagnetic conditions, the rate of cellular respiration also increased due to complex I, including that in the sperm of flies receiving essential phospholipids. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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14 pages, 3944 KiB

Open AccessArticle

Sperm Motility of Mice under Simulated Microgravity and Hypergravity

by Irina V. Ogneva, Maria A. Usik, Nikolay S. Biryukov and Yuliya S. Zhdankina

Int. J. Mol. Sci. 2020, 21(14), 5054; https://doi.org/10.3390/ijms21145054 - 17 Jul 2020

Cited by 20 | Viewed by 3832

Abstract

For deep space exploration, reproductive health must be maintained to preserve the species. However, the mechanisms underlying the effect of changes in gravity on male germ cells remain poorly understood. The aim of this study was to determine the effect of simulated micro- [...] Read more.

For deep space exploration, reproductive health must be maintained to preserve the species. However, the mechanisms underlying the effect of changes in gravity on male germ cells remain poorly understood. The aim of this study was to determine the effect of simulated micro- and hypergravity on mouse sperm motility and the mechanisms of this change. For 1, 3 and 6 h, mouse sperm samples isolated from the caudal epididymis were subjected to simulated microgravity using a random position machine and 2g hypergravity using a centrifuge. The experimental samples were compared with static and dynamic controls. The sperm motility and the percentage of motile sperm were determined using microscopy and video analysis, cell respiration was determined by polarography, the protein content was assessed by Western blotting and the mRNA levels were determined using qRT-PCR. The results indicated that hypergravity conditions led to more significant changes than simulated microgravity conditions: after 1 h, the speed of sperm movement decreased, and after 3 h, the number of motile cells began to decrease. Under the microgravity model, the speed of movement did not change, but the motile spermatozoa decreased after 6 h of exposure. These changes are likely associated with a change in the structure of the microtubule cytoskeleton, and changes in the energy supply are an adaptive reaction to changes in sperm motility. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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16 pages, 2358 KiB

Open AccessArticle

Antioxidant Strategy to Prevent Simulated Microgravity-Induced Effects on Bone Osteoblasts

by Caterina Morabito, Simone Guarnieri, Alessandra Cucina, Mariano Bizzarri and Maria A. Mariggiò

Int. J. Mol. Sci. 2020, 21(10), 3638; https://doi.org/10.3390/ijms21103638 - 21 May 2020

Cited by 28 | Viewed by 3466

Abstract

The effects induced by microgravity on human body functions have been widely described, in particular those on skeletal muscle and bone tissues. This study aims to implement information on the possible countermeasures necessary to neutralize the oxidative imbalance induced by microgravity on osteoblastic [...] Read more.

The effects induced by microgravity on human body functions have been widely described, in particular those on skeletal muscle and bone tissues. This study aims to implement information on the possible countermeasures necessary to neutralize the oxidative imbalance induced by microgravity on osteoblastic cells. Using the model of murine MC3T3-E1 osteoblast cells, cellular morphology, proliferation, and metabolism were investigated during exposure to simulated microgravity on a random positioning machine in the absence or presence of an antioxidant—the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our results confirm that simulated microgravity-induced morphological and metabolic alterations characterized by increased levels of reactive oxygen species and a slowdown of the proliferative rate. Interestingly, the use of Trolox inhibited the simulated microgravity-induced effects. Indeed, the antioxidant-neutralizing oxidants preserved cell cytoskeletal architecture and restored cell proliferation rate and metabolism. The use of appropriate antioxidant countermeasures could prevent the modifications and damage induced by microgravity on osteoblastic cells and consequently on bone homeostasis. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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12 pages, 983 KiB

Open AccessArticle

Dynamic Changes of Heart Failure Biomarkers in Response to Parabolic Flight

by Peter Jirak, Bernhard Wernly, Michael Lichtenauer, Vera Paar, Marcus Franz, Thorben Knost, Thaer Abusamrah, Malte Kelm, Johanna M. Muessig, Nana-Yaw Bimpong-Buta and Christian Jung

Int. J. Mol. Sci. 2020, 21(10), 3467; https://doi.org/10.3390/ijms21103467 - 14 May 2020

Cited by 8 | Viewed by 2541

Abstract

Background: we aimed at investigating the influence of weightlessness and hypergravity by means of parabolic flight on the levels of the heart failure biomarkers H-FABP, sST2, IL-33, GDF-15, suPAR and Fetuin-A. Methods: 14 healthy volunteers (males: eight; mean age: 28.9) undergoing 31 short-term [...] Read more.

Background: we aimed at investigating the influence of weightlessness and hypergravity by means of parabolic flight on the levels of the heart failure biomarkers H-FABP, sST2, IL-33, GDF-15, suPAR and Fetuin-A. Methods: 14 healthy volunteers (males: eight; mean age: 28.9) undergoing 31 short-term phases of weightlessness and hypergravity were included. At different time points (baseline, 1 h/24 h after parabolic flight), venous blood was drawn and analyzed by the use of ELISA. Results: sST2 evidenced a significant decrease 24 h after parabolic flight (baseline vs. 24, p = 0.009; 1 h vs. 24 h, p = 0.004). A similar finding was observed for GDF-15 (baseline vs. 24 h, p = 0.002; 1 h vs. 24 h, p = 0.025). The suPAR showed a significant decrease 24 h after parabolic flight (baseline vs. 24 h, p = 0.1726; 1 h vs. 24 h, p = 0.009). Fetuin-A showed a significant increase at 1 h and 24 h after parabolic flight (baseline vs. 24 h, p = 0.007; 1 h vs. 24 h, p = 0.04). H-FABP and IL-33 showed no significant differences at all time points. Conclusion: Our results suggest a reduction in cardiac stress induced by exposure to gravitational changes. Moreover, our findings indicate an influence of gravitational changes on proliferative processes and calcium homeostasis. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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Review

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17 pages, 837 KiB

Open AccessReview

The Effect of Space Travel on Bone Metabolism: Considerations on Today’s Major Challenges and Advances in Pharmacology

by Shirley Genah, Monica Monici and Lucia Morbidelli

Int. J. Mol. Sci. 2021, 22(9), 4585; https://doi.org/10.3390/ijms22094585 - 27 Apr 2021

Cited by 33 | Viewed by 11811

Abstract

Microgravity-induced bone loss is currently a significant and unresolved health risk for space travelers, as it raises the likelihood for irreversible changes that weaken skeletal integrity and the incremental onset of fracture injuries and renal stone formation. Another issue related to bone tissue [...] Read more.

Microgravity-induced bone loss is currently a significant and unresolved health risk for space travelers, as it raises the likelihood for irreversible changes that weaken skeletal integrity and the incremental onset of fracture injuries and renal stone formation. Another issue related to bone tissue homeostasis in microgravity is its capacity to regenerate following fractures due to weakening of the tissue and accidental events during the accomplishment of particularly dangerous tasks. Today, several pharmacological and non-pharmacological countermeasures to this problem have been proposed, including physical exercise, diet supplements and administration of antiresorptive or anabolic drugs. However, each class of pharmacological agents presents several limitations as their prolonged and repeated employment is not exempt from the onset of serious side effects, which limit their use within a well-defined range of time. In this review, we will focus on the various countermeasures currently in place or proposed to address bone loss in conditions of microgravity, analyzing in detail the advantages and disadvantages of each option from a pharmacological point of view. Finally, we take stock of the situation in the currently available literature concerning bone loss and fracture healing processes. We try to understand which are the critical points and challenges that need to be addressed to reach innovative and targeted therapies to be used both in space missions and on Earth. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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18 pages, 4041 KiB

Open AccessReview

Gravitational Experimental Platform for Animal Models, a New Platform at ESA’s Terrestrial Facilities to Study the Effects of Micro- and Hypergravity on Aquatic and Rodent Animal Models

by Julie Bonnefoy, Stéphanie Ghislin, Jérôme Beyrend, Florence Coste, Gaetano Calcagno, Isabelle Lartaud, Guillemette Gauquelin-Koch, Sylvain Poussier and Jean-Pol Frippiat

Int. J. Mol. Sci. 2021, 22(6), 2961; https://doi.org/10.3390/ijms22062961 - 15 Mar 2021

Cited by 14 | Viewed by 3559

Abstract

Using rotors to expose animals to different levels of hypergravity is an efficient means of understanding how altered gravity affects physiological functions, interactions between physiological systems and animal development. Furthermore, rotors can be used to prepare space experiments, e.g., conducting hypergravity experiments to [...] Read more.

Using rotors to expose animals to different levels of hypergravity is an efficient means of understanding how altered gravity affects physiological functions, interactions between physiological systems and animal development. Furthermore, rotors can be used to prepare space experiments, e.g., conducting hypergravity experiments to demonstrate the feasibility of a study before its implementation and to complement inflight experiments by comparing the effects of micro- and hypergravity. In this paper, we present a new platform called the Gravitational Experimental Platform for Animal Models (GEPAM), which has been part of European Space Agency (ESA)’s portfolio of ground-based facilities since 2020, to study the effects of altered gravity on aquatic animal models (amphibian embryos/tadpoles) and mice. This platform comprises rotors for hypergravity exposure (three aquatic rotors and one rodent rotor) and models to simulate microgravity (cages for mouse hindlimb unloading and a random positioning machine (RPM)). Four species of amphibians can be used at present. All murine strains can be used and are maintained in a specific pathogen-free area. This platform is surrounded by numerous facilities for sample preparation and analysis using state-of-the-art techniques. Finally, we illustrate how GEPAM can contribute to the understanding of molecular and cellular mechanisms and the identification of countermeasures. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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21 pages, 1915 KiB

Open AccessReview

The Emerging Role of Macrophages in Immune System Dysfunction under Real and Simulated Microgravity Conditions

by Yulong Sun, Yuanyuan Kuang and Zhuo Zuo

Int. J. Mol. Sci. 2021, 22(5), 2333; https://doi.org/10.3390/ijms22052333 - 26 Feb 2021

Cited by 20 | Viewed by 4122

Abstract

In the process of exploring space, the astronaut’s body undergoes a series of physiological changes. At the level of cellular behavior, microgravity causes significant alterations, including bone loss, muscle atrophy, and cardiovascular deconditioning. At the level of gene expression, microgravity changes the expression [...] Read more.

In the process of exploring space, the astronaut’s body undergoes a series of physiological changes. At the level of cellular behavior, microgravity causes significant alterations, including bone loss, muscle atrophy, and cardiovascular deconditioning. At the level of gene expression, microgravity changes the expression of cytokines in many physiological processes, such as cell immunity, proliferation, and differentiation. At the level of signaling pathways, the mitogen-activated protein kinase (MAPK) signaling pathway participates in microgravity-induced immune malfunction. However, the mechanisms of these changes have not been fully elucidated. Recent studies suggest that the malfunction of macrophages is an important breakthrough for immune disorders in microgravity. As the first line of immune defense, macrophages play an essential role in maintaining homeostasis. They activate specific immune responses and participate in large numbers of physiological activities by presenting antigen and secreting cytokines. The purpose of this review is to summarize recent advances on the dysfunction of macrophages arisen from microgravity and to discuss the mechanisms of these abnormal responses. Hopefully, our work will contribute not only to the future exploration on the immune system in space, but also to the development of preventive and therapeutic drugs against the physiological consequences of spaceflight. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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19 pages, 14769 KiB

Open AccessReview

Implications of Altered Endosome and Lysosome Biology in Space Environments

by Ian R. D. Johnson, Catherine T. Nguyen, Petra Wise and Daniela Grimm

Int. J. Mol. Sci. 2020, 21(21), 8205; https://doi.org/10.3390/ijms21218205 - 2 Nov 2020

Cited by 8 | Viewed by 5757

Abstract

Space exploration poses multiple challenges for mankind, not only on a technical level but also to the entire physiology of the space traveller. The human system must adapt to several environmental stressors, microgravity being one of them. Lysosomes are ubiquitous to every cell [...] Read more.

Space exploration poses multiple challenges for mankind, not only on a technical level but also to the entire physiology of the space traveller. The human system must adapt to several environmental stressors, microgravity being one of them. Lysosomes are ubiquitous to every cell and essential for their homeostasis, playing significant roles in the regulation of autophagy, immunity, and adaptation of the organism to changes in their environment, to name a few. Dysfunction of the lysosomal system leads to age-related diseases, for example bone loss, reduced immune response or cancer. As these conditions have been shown to be accelerated following exposure to microgravity, this review elucidates the lysosomal response to real and simulated microgravity. Microgravity activates the endo-lysosomal system, with resulting impacts on bone loss, muscle atrophy and stem cell differentiation. The investigation of lysosomal adaptation to microgravity can be beneficial in the search for new biomarkers or therapeutic approaches to several disease pathologies on earth as well as the potential to mitigate pathophysiology during spaceflight. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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22 pages, 3167 KiB

Open AccessReview

Breast Cancer Cells in Microgravity: New Aspects for Cancer Research

by Mohamed Zakaria Nassef, Daniela Melnik, Sascha Kopp, Jayashree Sahana, Manfred Infanger, Ronald Lützenberg, Borna Relja, Markus Wehland, Daniela Grimm and Marcus Krüger

Int. J. Mol. Sci. 2020, 21(19), 7345; https://doi.org/10.3390/ijms21197345 - 5 Oct 2020

Cited by 21 | Viewed by 6348

Abstract

Breast cancer is the leading cause of cancer death in females. The incidence has risen dramatically during recent decades. Dismissed as an “unsolved problem of the last century”, breast cancer still represents a health burden with no effective solution identified so far. Microgravity [...] Read more.

Breast cancer is the leading cause of cancer death in females. The incidence has risen dramatically during recent decades. Dismissed as an “unsolved problem of the last century”, breast cancer still represents a health burden with no effective solution identified so far. Microgravity (µg) research might be an unusual method to combat the disease, but cancer biologists decided to harness the power of µg as an exceptional method to increase efficacy and precision of future breast cancer therapies. Numerous studies have indicated that µg has a great impact on cancer cells; by influencing proliferation, survival, and migration, it shifts breast cancer cells toward a less aggressive phenotype. In addition, through the de novo generation of tumor spheroids, µg research provides a reliable in vitro 3D tumor model for preclinical cancer drug development and to study various processes of cancer progression. In summary, µg has become an important tool in understanding and influencing breast cancer biology. Full article

(This article belongs to the Special Issue Microgravity and Space Medicine)

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