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Integrated Research Plan to Assess the Combined Effects of Space Radiation, Altered Gravity, and Isolation and Confinement on Crew Health and Performance: Problem Statement

Future crewed exploration missions to Mars could last up to three years and will expose astronauts to unprecedented environmental challenges. Challenges to the nervous system during these missions will include factors of: space radiation that can damage sensitive neurons in the central nervous system (CNS); isolation and confinement can affect cognition and behavior; and altered gravity that will change the astronauts’ perception of their environment and their spatial orientation, and will affect their coordination, balance, and locomotion. In the past, effects of spaceflight stressors have been characterized individually. However, long-term, simultaneous exposure to multiple stressors will produce a range of interrelated behavioral and biological effects that have the potential to adversely affect operationally relevant crew performance. These complex environmental challenges might interact synergistically and increase the overall risk to the health and performance of the astronaut. Therefore, NASA’s Human Research Program (HRP) has directed an integrated approach to characterize and mitigate the risk to the CNS from simultaneous exposure to these multiple spaceflight factors. The proposed research strategy focuses on systematically evaluating the relationships among three existing research risks associated with spaceflight: Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation (CNS), Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders (BMed), and Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight (SM). NASA’s HRP approach is intended to identify the magnitude and types of interactions as they affect behavior, especially as it relates to operationally relevant performance (e.g., performance that depends on reaction time, procedural memory, etc.). In order to appropriately characterize this risk of multiple spaceflight environmental stressors, there is a recognition of the need to leverage research approaches using appropriate animal models and behavioral constructs. Very little has been documented on the combined effects of altered gravity, space radiation, and other psychological and cognitive stressors on the CNS. Preliminary evidence from rodents suggest that a combination of a minimum of exposures to even two of three stressors of: simulated space radiation, simulated microgravity, and simulated isolation and confinement, have produced different and more pronounced biological and performance effects than exposure to these same stressors individually. Structural and functional changes to the CNS of rodents exposed to transdisciplinary combined stressors indicate that important processes related to information processing are likely altered including impairment of exploratory and risk taking behaviors, as well as executive function including learning, memory, and cognitive flexibility — all of which may be linked to changes in related operational relevant performance. The fully integrated research plan outlines approaches to evaluate how combined, potentially synergistic, impacts of simultaneous exposures to spaceflight hazards will affect an astronaut’s CNS and their operationally relevant performance during future exploration missions, including missions to the Moon and Mars. The ultimate goals are to derive risk estimates for the combined, potentially synergistic, effects of the three major spaceflight hazards that will establish acceptable maximum decrement or change in a physiological or behavioral parameters during or after spaceflight, the acceptable limit of exposure to a spaceflight factor, and to evaluate strategies to mitigate any associated decrements in operationally relevant performance.

Steinberg, Susan L.↗

Integrated Research Plan to Assess the Combined Effects of Space Radiation, Altered Gravity, and Isolation and Confinement on Crew Health and Performance: Implementation Strategy

This document supplements the white paper titled CBS Integrated Research Plan: Problem Statement. The Problem Statement describes why it is important to implement a fully integrated research plan to derive risk estimates for the combined, potentially synergistic, effects of the three major spaceflight hazards (space radiation; isolated, confined, and extreme environments; altered gravity). These risk estimates will help establish acceptable maximum decrement or change in a physiological or behavioral parameter during or after spaceflight, and the acceptable limit of exposure to the combined spaceflight hazards. This Implementation Strategy describes how the research plan will accomplish the CBS Integrated Research Plan goals. The Implementation Strategy includes approaches to evaluate relationships among biological responses underlying three risks that are managed by three of NASA’s Human Research Project (HRP) organizational “elements”. This CBS (Acute effects of radiation on CNS, BMed, Sensorimotor) Integrated Research Plan also identifies strategies to monitor and mitigate decrements to operationally relevant performance. Currently, the strategy that was initiated in 2018, includes an eight-year research plan and a four-year validation plan that extend to the year 2030. Once the monitoring tools and countermeasures are developed, they will be validated and refined during four years of early exploration missions. The planned tasks and their associated research products and deliverables have been mapped to the individual research emphases to clearly demonstrate how each research area helps ensure crew health and safety during exploration missions.

Susan Steinberg↗

Short-term memory and dual task performance

Two hypotheses concerning the way in which short-term memory interacts with another task in a dual task situation are considered. It is noted that when two tasks are combined, the activity of controlling and organizing performance on both tasks simultaneously may compete with either task for a resource; this resource may be space in a central mechanism or general processing capacity or it may be some task-specific resource. If a special relationship exists between short-term memory and control, especially if there is an identity relationship between short-term and a central controlling mechanism, then short-term memory performance should show a decrement in a dual task situation. Even if short-term memory does not have any particular identity with a controlling mechanism, but both tasks draw on some common resource or resources, then a tradeoff between the two tasks in allocating resources is possible and could be reflected in performance. The persistent concurrence cost in memory performance in these experiments suggests that short-term memory may have a unique status in the information processing system.

Regan, J. E.↗

Effect of Carbon Dioxide Exposure on Physical and Cognitive Performance in a Simulated Spaceflight Contingency Scenario

Introduction: Carbon dioxide (CO2) produced by astronauts inside space suits can accumulate to levels that affect health and performance. The human health and performance risks associated with different levels of CO2 exposure in the flight environment remain an area of debate. The purpose of this study is to characterize the limit of acceptable performance (cognitive and physical) decrements and symptom severity for mission operations when subjected to elevated inspired CO2 levels in the spacesuit during contingency EVA scenarios. Methods: This study will create a simulation of a 1-hour contingency EVA walk back to the habitat, incorporating a passive treadmill and a fully immersive virtual reality (VR) simulation of a lunar EVA. Subjects will be asked to walk on a treadmill while breathing partial pressures of CO2 of 0, 5, 10, 15, 20, 25, 30mmHg for 1 hour at a time. Cognitive performance will be quantified using validated cognitive tests and measures of functional task performance embedded within the VR environment. Test subject symptoms and self-assessment of performance will be evaluated via survey. Results: This study currently has approval from NASA’s Institutional Review Board and has completed the Test Readiness Review process. Next steps for this research study include test subject recruitment, data collection, and analysis. Data collection is planned for calendar year 2022 and 2023. Discussion: This study will provide valuable information regarding how various partial pressures of CO2 exposure impact acute health, as well as cognitive and physical performance during simulated lunar EVA. This information will be vital in the assessment of overall risk associated with current hardware (vehicle and suit) design for upcoming exploration missions. It will also be invaluable for informing future standards and requirements.

carbon dioxide↗

Effect of Carbon Dioxide Exposure on Physical and Cognitive Performance in A Simulated Spaceflight Contingency Scenario

INTRODUCTION: Carbon dioxide (CO2) produced by astronauts inside space suits can accumulate to levels that may affect health and performance. The human health and performance risks associated with different levels of CO2 exposure in the flight environment remain an area of debate. The purpose of this study is to characterize the limit of acceptable performance (cognitive and physical) decrements and symptom severity for mission operations when subjected to elevated inspired CO2 levels in simulated contingency lunar extravehicular activity (EVA) scenarios. METHODS: This study will create a simulation of a 1-hour, ~2km contingency EVA walk back to a habitat, incorporating a passive treadmill and a fully immersive virtual reality (VR) simulation of a lunar EVA environment. Subjects will be asked to walk on a treadmill while breathing partial pressures of CO2 of 0, 5, 10, 15, 20, 25, 30mmHg for 1 hour at a time. Cognitive performance will be quantified using validated cognitive tests and measures of functional task performance embedded within the VR environment. Test subject symptoms and self-assessment of performance will be evaluated via survey. RESULTS: This study currently has approval from NASA’s Institutional Review Board and has completed the Test Readiness Review process. Next steps for this research study include test subject recruitment, data collection, and analysis. Data collection is planned for calendar year 2023 and 2024. DISCUSSION: This study will provide valuable information regarding how various partial pressures of CO2 exposure impact acute health, as well as cognitive and physical performance during simulated contingency lunar EVA. This information will enable assessment of health and performance risk associated with spacesuit systems and operations concepts for future exploration missions as well as informing definition of future standards and requirements.

D. M. Nusbaum↗

Effect of Carbon Dioxide Exposure on Physical and Cognitive Performance in A Simulated Spaceflight Contingency Scenario

INTRODUCTION: Carbon dioxide (CO2) produced by astronauts inside space suits can accumulate to levels that may affect health and performance. The human health and performance risks associated with different levels of CO2 exposure in the flight environment remain an area of debate. The purpose of this study is to characterize the limit of acceptable performance (cognitive and physical) decrements and symptom severity for mission operations when subjected to elevated inspired CO2 levels in simulated contingency lunar extravehicular activity (EVA) scenarios. METHODS: This study will create a simulation of a 1-hour, ~2km contingency EVA walk back to a habitat, incorporating a passive treadmill and a fully immersive virtual reality (VR) simulation of a lunar EVA environment. Subjects will be asked to walk on a treadmill while breathing partial pressures of CO2 of 0, 5, 10, 15, 20, 25, 30mmHg for 1 hour at a time. Cognitive performance will be quantified using validated cognitive tests and measures of functional task performance embedded within the VR environment. Test subject symptoms and self-assessment of performance will be evaluated via survey. RESULTS: This study currently has approval from NASA’s Institutional Review Board and has completed the Test Readiness Review process. Next steps for this research study include test subject recruitment, data collection, and analysis. Data collection is planned for calendar year 2023 and 2024. DISCUSSION: This study will provide valuable information regarding how various partial pressures of CO2 exposure impact acute health, as well as cognitive and physical performance during simulated contingency lunar EVA. This information will enable assessment of health and performance risk associated with spacesuit systems and operations concepts for future exploration missions as well as informing definition of future standards and requirements.

carbon dioxide↗

Teams in Space: Knowledge Gained, but More to Explore

NASA’s Human Research Program oversees the Team Risk (i.e., Risk of Performance and Behavioral Health Decrements due to Inadequate Cooperation, Coordination, Communication and Psychosocial Adaptation within a Team). Research in this area informs all aspects of an astronaut’s career, from hiring to training to mission support, and works to address new challenges related to lunar and Mars missions. NASA’s astronaut selection process creates an astronaut corps of highly qualified, team-oriented individuals, which allows mission planners much flexibility in composing small crews for specific missions. These crews are further developed and supported through extensive training, including team skills training, and countermeasures available to the crew throughout the mission. However, in the high consequence environment of long-duration missions, team composition is complex and is not a one-time concern to be addressed pre-mission. Team factors such as team cohesion, dyadic relationships, and shared team cognition are likely to change dynamically in response to each interaction and event experienced by the individuals and the team as a whole. Thus, monitoring and optimizing team composition at a more micro level (e.g., per task) is one way to support team functioning and performance. Spaceflight teams research also includes the multi-team system of Mission Control and coordination between space-to-ground, adding another avenue in which risk might be introduced, particularly under exploration missions that experience significant communication delays. Spaceflight teams research has recently experienced a concentrated flurry of analog research over the past decade, shedding light on the many unique challenges and potential solutions to mitigate the team risk in long-duration exploration missions. However, questions still remain about how to, for example, create unobtrusive operational measures and how to advance interdisciplinary teams research and countermeasure development. We present an overview of the challenges facing teams in space, our current knowledge, and the next steps for research and spaceflight operations.

Lauren Blackwell Landon↗

Astronauts Need Their Rest Too: Sleep-Wake Actigraphy and Light Exposure During Space Flight

The success and effectiveness of human space flight depends on astronauts' ability to maintain a high level of cognitive performance and vigilance. This alert state ensures the proper operation of sophisticated instrumentation. An important way for humans to remedy fatigue and maintain alertness is to get plenty of rest. Astronauts, however, commonly experience difficulty sleeping while in space. During flight, they may also experience disruption of the body's circadian rhythm - the natural phases the body goes through every day as we oscillate between states of high activity during the waking day and recuperation, rest, and repair during nighttime sleep. Both of these factors are associated with impairment of alertness and performance, which could have important consequences during a mission in space. The human body was designed to sleep at night and be alert and active during the day. We receive these cues from the time of day or amount of light, such as the rising or setting of the sun. However, in the environment of the Space Shuttle or the International Space Station where light levels are highly variable, the characteristics of a 24-hour light/dark cycle are not present to cue the astronauts' bodies about what time of the day it is. Astronauts orbiting Earth see a sunset and sunrise every 90 minutes, sending potentially disruptive signals to the area of the brain that regulates sleep. On STS-107, researchers will measure sleep-wake activity with state-of-the-art technology to quantify how much sleep astronauts obtain in space. Because light is the most powerful time cue to the body's circadian system, individual light exposure patterns of the astronauts will also be monitored to determine if light exposure is associated with sleep disruption. The results of this research could lead to the development of a new treatment for sleep disturbances, enabling crewmembers to avoid the decrements in alertness and performance due to sleep deprivation. What we learn about sleep in space informs treatment for earthbound populations, such as the elderly and insomniacs, who experience frequent sleep disturbances or altered sleep patterns.

Czeisler, Charles↗

Human performance and physiological function during a 24-hr exposure to 1 percent bromotrifluoromethane (Halon 1301)

Performance and physiological measurements were obtained from four pairs of men exposed for 24 hr to 1 percent (10,000 ppm) Halon 1301 (CBrF3) and to air with order counterbalanced using a double-blind protocol. Cognitive and motor performance was assessed before, during, and after the exposures, using seven scales of the Automated Portable Testing System, which produced 13 measures of performance. Halon inhalation induced decrements in 2 of the 13 measures, but actual and estimated magnitudes of the decrements were no greater than 5 percent of baseline values. Physiological data obtained before, during, and after the exposures revealed significant changes during Halon inhalation for 6 of the 52 variables assessed; however, all physiological values remained within clinically acceptable limits. No cardiovascular effects were noted. This study demonstrated that exposure to 1 percent Halon 1301 for 24 hr can produce minor disturbance of central nervous system function as assessed by cognitive tasks.

Calkins, D. S.↗

Human performance and physiological function during a 24-hr exposure to 1% bromotrifluoromethane (Halon 1301)

Performance and physiological measurements were obtained from four pairs of men exposed for 24 hr to 1% (10,000 ppm) Halon 1301 (bromotrifluoromethane, CBrF3) and to air with order counterbalanced using a double-blind protocol. Cognitive and motor performance was assessed before, during, and after the exposures using seven scales of the Automated Portable Testing System, which produced 13 measures of performance. Halon inhalation induced decrements in 2 of the 13 measures, but actual and estimated magnitudes of the decrements were no greater than 5% of baseline values. Physiological data were obtained before, during, and after the exposures from clinical chemistry analyses of blood and urine samples, pulmonary function tests, and monitoring of vital signs. Significant change during Halon inhalation was observed for 6 of the 52 variables assessed; however, all physiological values remained within clinically acceptable limits. No cardiovascular effects were noted. This study demonstrated that exposure to 1% Halon 1301 for 24 hr can produce minor disturbance of central nervous system function as assessed by cognitive tasks.

Randomized Controlled Trial↗

The Artificial Gravity Bed Rest Pilot Project: Effects on Knee Extensor and Plantar Flexor Muscle Groups

The goal of this project was to examine the effects of artificial gravity (2.5 g) on skeletal muscle strength and key anabolic/catabolic markers known to regulate muscle mass. Two groups of subjects were selected for study: 1) a 21 day-bed rest (BR) control (C) group (N=7); and 2) an AG group (N=8), which was exposed to 21 days of bed-rest plus daily 1 hr exposures to AG (2.5 g). This particular experiment was part of an integrated AG Pilot Project sponsored by NASA/Johnson Space Center. The in vivo torque-velocity relationships of the knee extensors and plantar flexors of the ankle were determined pre and post treatment. Also, pre- and post treatment biopsy samples were obtained from both the vastus lateralis and soleus muscles and were used, in part, for a series of analyses on gene expression (mRNA abundance) of key factors implicated in the anabolic versus catabolic state of the muscle. Post/Pre toque-velocity determinations revealed greater decrements in knee extensor performance in the C versus AG group (P less than 0.04). The plantar flexor muscle group of the AG subjects actually demonstrated a net gain in torque-velocity relationship; whereas, in the C group the overall post/pre responses declined (AG vs C; P less than 0.001). Measurements of muscle fiber cross-sectional area (for both muscles) demonstrated a loss of approx. 20% in the C group while no losses were evident in the AG group. RT-PCR analyses of muscle biopsy specimens demonstrated that markers of growth and cytoskeletal integrity (IGF-1, IGF-1 BP4, mechano growth factor, total RNA, and pro-collagen 3a) were higher in the AG group, whereas catabolic markers (myostatin and atrogen) were elevated in the C group. Importantly, these patterns were seen in both muscles. Based on these observations we conclude that paradigms of AG have the potential to maintain the functional, biochemical, and structural homeostasis of skeletal muscle in the face of chronic unloading states. These findings also warrant further studies since it is likely that other robust paradigms of AG that employ various exercise strategies may be more effective in counteracting long duration unloading states as anticipated on the platforms of the Moon and Mars.

Caiozzo, V. J.↗

Myotonometry as a Surrogate Measure of Muscle Strength

Space flight-induced muscle atrophy/neuromuscular degradation and the consequent decrements in crew-member performance are of increasing concern as mission duration lengthens, and planetary exploration after extended space flight is planned. Pre- to post-flight strength measures have demonstrated that specific countermeasures, such as resistive exercise, are effective at countering microgravity-induced muscle atrophy and preventing decrements in muscle strength. However, in-flight assessment/monitoring of exercise countermeasure effectiveness will be essential during exploration class missions due to their duration. The ability to modify an exercise countermeasure prescription based on such real-time information will allow each individual crew member to perform the optimal amount and type of exercise countermeasure to maintain performance. In addition, such measures can be used to determine if a crew member is physically capable of performing a particular mission-related task during exploration class missions. The challenges faced in acquiring such data are those common to all space operations, namely the requirement for light-weight, low power, mechanically reliable technologies that make valid measurements in microgravity, in this case of muscle strength/neuromuscular function. Here we describe a simple, light-weight, low power, non-invasive device, known as the Myotonometer, that measures tissue stiffness as an indirect measure of muscle contractile state and muscle force production. Repeat myotonometer measurements made at the same location on the surface of the rectis femoris muscle (as determined using a 3D locator device, SEM plus or minus 0.34 mm) were shown to be reproducible over time at both maximal voluntary contraction (MVC) and at rest in a total of 17 sedentary subjects assessed three times over a period of seven days. In addition, graded voluntary isometric force production (i.e. 20%, 40%, 60%, 80% & 100% of MVC) during knee extension was shown to be significantly (p less than 0.01) correlated with contemporaneous myotonometer measurements made on the rectis femoris muscle in a total of 16 healthy subjects (8 males, 8 females). Further-more, this device has been operationally tested during parabolic flight demonstrating its suitability for use in a microgravity environment. Our data indicates that the Myotonometer is a viable surrogate measure of muscle contractile state/tone and of muscle strength/force production. Additional studies are required to assess the suitability of this technique for assessing these measures in de-conditioned subjects such as crew-members.

Ang, B. S.↗

Motion effects on an IFR hovering task: Analytical predictions and experimental results

An analytical pilot model incorporating the effects of motion cues and display scanning and sampling is tested by comparing predictions against experimental results on a moving base simulator. The simulated task is that of precision hovering of a VTOL having varying amounts of rate damping, and using separated instrument displays. Motion cue effects are investigated by running the experiment under fixed and moving base conditions, the latter in two modes; full motion, and angular motion only. Display scanning behavior is measured on some of the runs. The results of the program show that performance is best with angular motion only, most probably because a g-vector tilt cue is available to the pilot in this motion condition. This provides an attitude indication even when not visually fixating the attitude display. Vestibular threshold effects are also present in the results because of the display scaling used to permit hovering position control within the motion simulator limits; no washouts are used in the simulator drive signals. The IFR nature of the task results in large decrements in pilot opinion and performance relative to VFR conditions because of the scanning workload. Measurements of scanning behavior are sensitive to motion conditions and show more attention to attitude control under fixed base conditions.

Ringland, R. F.↗

An Evaluation of the Frequency and Severity of Motion Sickness Incidences in Personnel Within the Command and Control Vehicle (C2V)

The purpose of this study was to assess the frequency and severity of motion sickness in personnel during a field exercise in the Command and Control Vehicle (C2V). This vehicle contains four workstations where military personnel are expected to perform command decisions in the field during combat conditions. Eight active duty military men (U.S. Army) at the Yuma Proving Grounds in Arizona participated in this study. All subjects were given baseline performance tests while their physiological responses were monitored on the first day. On the second day of their participation, subjects rode in the C2V while their physiological responses and performance measures were recorded. Self-reports of motion sickness were also recorded. Results showed that only one subject experienced two incidences of emesis. However, seven out of the eight subjects reported other motion sickness symptoms; most predominant was the report of drowsiness, which occurred a total of 19 times. Changes in physiological responses were observed relative to motion sickness symptoms reported and the different environmental conditions (i.e., level, hills, gravel) during the field exercise. Performance data showed an overall decrement during the C2V exercise. These findings suggest that malaise and severe drowsiness can potentially impact the operational efficiency of the C2V crew. It was concluded that conflicting sensory information from the subject's visual displays and movements of the vehicle during the field exercise significantly contributed to motion sickness symptoms. It was recommended that a second study be conducted to further evaluate the impact of seat position or orientation and C2V experience on motion sickness susceptibility. Further, it was recommended that an investigation be performed on behavioral methods for improving crew alertness, motivation, and performance and for reducing malaise.

Cowings, Patricia S.↗

Assessment of Spatial Navigation and Docking Performance During Simulated Rover Tasks

INTRODUCTION: Following long-duration exploration transits, pressurized rovers will enhance surface mobility to explore multiple sites across Mars and other planetary bodies. Multiple rovers with docking capabilities are envisioned to expand the range of exploration. However, adaptive changes in sensorimotor and cognitive function may impair the crew s ability to safely navigate and perform docking tasks shortly after transition to the new gravitoinertial environment. The primary goal of this investigation is to quantify post-flight decrements in spatial navigation and docking performance during a rover simulation. METHODS: Eight crewmembers returning from the International Space Station will be tested on a motion simulator during four pre-flight and three post-flight sessions over the first 8 days following landing. The rover simulation consists of a serial presentation of discrete tasks to be completed within a scheduled 10 min block. The tasks are based on navigating around a Martian outpost spread over a 970 sq m terrain. Each task is subdivided into three components to be performed as quickly and accurately as possible: (1) Perspective taking: Subjects use a joystick to indicate direction of target after presentation of a map detailing current orientation and location of the rover with the task to be performed. (2) Navigation: Subjects drive the rover to the desired location while avoiding obstacles. (3) Docking: Fine positioning of the rover is required to dock with another object or align a camera view. Overall operator proficiency will be based on how many tasks the crewmember can complete during the 10 min time block. EXPECTED RESULTS: Functionally relevant testing early post-flight will develop evidence regarding the limitations to early surface operations and what countermeasures are needed. This approach can be easily adapted to a wide variety of simulated vehicle designs to provide sensorimotor assessments for other operational and civilian populations.

Wood, S. J.↗

The influence of ship motion of manual control skills

The effects of ship motion on a range of typical manual control skills were examined on the Warren Spring ship motion simulator driven in heave, pitch, and roll by signals taken from the frigate HMS Avenger at 13 m/s (25 knots) into a force 4 wind. The motion produced a vertical r.m.s. acceleration of 0.024g, mostly between 0.1 and 0.3 Hz, with comparatively little pitch or roll. A task involving unsupported arm movements was seriously affected by the motion; a pursuit tracking task showed a reliable decrement although it was still performed reasonably well (pressure and free moving tracking controls were affected equally by the motion); a digit keying task requiring ballistic hand movements was unaffected. There was no evidence that these effects were caused by sea sickness. The differing response to motion of the different tasks, from virtual destruction to no effect, suggests that a major benefit could come from an attempt to design the man/control interface onboard ship around motion resistant tasks.

Mcleod, P.↗

Exercise-training protocols for astronauts in microgravity

Based on physical working requirements for astronauts during intra- and extravehicular activity and on the findings from bed-rest studies that utilized exercise training as a countermeasure for the reduction of aerobic power, deterioration of muscular strength and endurance, decrements in mood and cognitive performance, and possibly for bone loss, two exercise protocols are proposed. One assumes that, during microgravity, astronaut exercise physiological functions should be maintained at 100 percent of ground-based levels. The other assumes that maximal aerobic power in flight can be reduced by 10 percent of the ground-based level.

Greenleaf, J. E.↗

Human placenta-derived stromal cells mitigate select immune responses to simulated weightlessness

Space flight presents unique risks to human health. Microgravity and social isolation are important space flight stressors which have vast impact on multiple systems such as the musculoskeletal, immune and central nervous system (CNS). To explore candidate countermeasures against tissue decrements caused by spaceflight, we performed a pilot study with PLacental-eXpanded stromal (PLX) cells. PLX cells secrete factors that modulate the immune system, but do not trigger host immune responses, enabling treatment in subjects that have intact immune systems. These cells had previous success in treating critical limb ischemia and acute radiation syndrome in murine models. In this study, 4-month-old female mice underwent 30 days of hindlimb unloading (HU) in single housing conditions to simulate long-term weightlessness and isolation. HU and normally ambulating controls were administered with PLX cells or sham-injected with Plasmalyte. We hypothesized that administration of PLX cells will mitigate some of the effects caused by prolonged HU. We found that treatment with PLX cells was well tolerated as indicated by body weights, circulating corticosterone levels and immune organ response to injection of the cells. HU led to the expected decreases in soleus muscle weights and bone loss. We did not observe any protective properties of the PLX cells in the musculoskeletal system but found that the cell treatment partially protected from a subset of HU-induced immune and CNS changes. In the hippocampus, protein levels of 9 of 44 cytokines were downregulated by HU. PLX administration mitigated changes in expression of 8 of these cytokines, including IL-2, IL-6 and MCP-1. To our knowledge, this is the first report on the protective effects of PLX-PAD against HU-induced changes in the cytokine milieu of the CNS. Our findings warrant further studies, which includes testing in actual spaceflight.

Microgravity↗