Translation from Microgravity Research to Earth Application

The topic "Translation from Microgravity Research to Earth Application" comprises publications focusing on space life sciences, gravitational biology and space medicine [...].

the different mechanisms and factors regulating the humoral crosstalk between muscle and bone [8]. The authors focused on the interplay between myokines and osteokines and their mutual regulation [8]. macrophage phenotypes (PT) All PT: decrease in TNF-α expression and an increase in IL-12 and VEGF expression IL-10 was significantly increased in M1 and M2 Insight in phenotypic macrophage function in µg Research Article [14] Reynolds et al. validated causal diagrams of human health risks for spaceflight and used as an example bone data from rodents [1]. They applied DAGs to determine the risk of bone fractures of rodents in space [1]. Ganse et al. [4] focused on comparable cartilage alterations in humans, animals and cells during spaceflight. The exposure to µg combined with radiation is likely to lead to joint cartilage thinning and degeneration and consequently to osteoarthritis after long-term space missions. Therefore, research on countermeasures is necessary with regard to future deep space exploration adventures to avoid or inhibit the development of osteoarthritis [4].
A further contribution studied the effects of µg provided by parabolic flight maneuvers on human chondrocytes [9]. The authors introduced a new experimental setup based on the fluorescent Ca 2+ reporter CaMPARI2, onboard LED arrays and subsequent microscopic analysis on the ground. CaMPARI2 showed a strong Ca 2+ response triggered by histamine, but it was not affected by the alternating gravitational load of a parabolic flight [9]. The tested system is suitable for environments with varying accelerations and is useful for future large-scale pathway analyses with pharmacological libraries [9].
One problem of a long-term spaceflight is the isolation of the space travelers, which can be simulated by long-term stays in Antarctica. Feuerecker et al. [6] reported on a one-year expedition in Antarctica. The individual expedition members showed increased or even new allergic reactions to environmental allergens after their return. Long-term confinement in the Antarctic seems to alter immune function, which is in some individuals pronounced after return to the familiar allergen environment [6], an interesting finding which has to be studied in detail in the future. So far, the dysfunction of the immune system of astronauts had been addressed by various studies [23]. Another publication of this topic reported changes in macrophages exposed to the Rotating Wall Vessel for three days [14]. In M0, M1 and M2 phenotypes, s-µg results in a decrease in TNF-expression and an increase in IL-12 and VEGF expression. IL-10 was also significantly increased in M1 and M2, but not M0 macrophages [14]. These data can improve our knowledge about macrophage function in s-µg, but validation under real spaceflight conditions is necessary. Another interesting study showed that collagen type XV is related to endoplasmic reticulum stress and inflammation of adipose tissue [13]. The FAK/integrin β1 signaling pathway and M1 macrophages are involved in this process and should be addressed in mice or rats exposed to s-µg or in space. Sarkar et al. [5] reviewed the current knowledge about bone marrow remodeling and dysfunction of the innate immune system in vitro and in vivo in space and with µg-simulation techniques. The importance of multicellular spheroids to answer immunological questions during and after future spaceflights was extensively discussed [5].
Two research articles focused on neurological changes induced by altered gravity conditions [2,12]. An in vitro study evaluated the impact of hypergravity to potentially modify key features of astrocyte reactivity [2]. Fundamental mechanisms on shape and mobility of astrocytes are affected due to increased gravitational stimulation (hypergravity). Lichterfeld et al. identified an attenuation of key features of astrocyte reactivity due to hypergravity exposure. This finding suggests hypergravity together with live-cell imaging as a tool for future studies with other cell types, organoids, 3D spheroids or ex vivo cultures [2]. The second neurological study used the hindlimb unloading model (HLU) to expose rats to s-µg for seven days and focused on the distribution of monoamines in functional territories of the rat brain [12]. The analyses reveal remodeling of the 5-HT (serotonin; 5-hydroxytryptamine) system alone or in interaction with catecholaminergic systems, notably DA (dopamine). This profile induced by HLU in Long Evans rats is able to confer a transient vulnerability for the development of neuropsychiatric diseases such as mood disorders [12]. Therefore, rehabilitation programs are applicable for space travelers for their return to Earth.
Long-term stays in space put space travelers at risk of developing serious health problems. Three further reviews of this topic discuss the recent knowledge about skin health [7], cardiovascular health problems [10] and cancer [11] for humans in space. An interesting review reports about stressors in space and skin health [7]. Such spaceflight stressors for the skin are µg, ionizing radiation and psychological stress and are associated with skin health problems [7]. To find countermeasures to protect astronaut's skin, simulation models and their combination have to be developed to study the effects of cosmic radiation, µg and psychological stress hormones. Baran et al. [10] summarized current research and knowledge in the field of space life sciences with a focus on the cardiovascular system in the real and simulated µg-environment. In early µg, the cephalad fluid shift increases the stroke volume (35-46%) and cardiac output (18-41%) in astronauts. Later decreases in arterial pressure are occurring and result in the development of cardiac atrophy in space [10]. Moreover, arrhythmias were reported. In vivo and in vitro models reveal cellular and molecular changes, including alterations in cell shape and endothelial dysfunction [24]. Finally, this topic covers a review about cancer in space [11]. There is still an unclear risk for cancer in astronauts. In vitro studies demonstrated that µg induces multicellular spheroid formation, cytoskeleton rearrangement, gene and protein expression changes and apoptosis [11,25]. Novel OMICs results suggest new biomarkers and drug targets useful to develop effective cancer treatments [25][26][27].
In summary, the excellent papers included in this topic report novel findings in the field of space life sciences research.
We would like to thank the authors who supported this topic. We are convinced that research on the International Space Station, in outer space, in extreme environments as well as methods for simulation of µg in combination with novel molecular biological technologies such as OMICs contribute toward the health protection and treatment of diseases of future space travelers who conquer the universe during deep space exploration missions to Moon and Mars. The results will be also translated to health issues on Earth.