Investigation of the potential interplay of spaceflight conditions on the skin

Human deep-space exploration is the ambitious goal of national space agencies to increase the ability of colonizing the Moon and Mars in the future. However, health risks for the astronauts are one of the main challenges to overcome in order to reach this goal. The field of space biological research investigates the effects of the hostile space environment on the human body. More specifically, in ground-based research on Earth, different techniques can be applied to simulate these conditions in order to elucidate harmful effects that should be taken into account when performing health risk assessments for astronauts during planned long-durations deep-space missions in the future. The aim of this thesis was to reveal the impact of space conditions on the skin and how they affect various aspects of the wound healing process. In particular, the potential interplay, that might be additive or synergistic, of simultaneous exposure of normal human dermal fibroblasts (NHDF) to space radiation, microgravity and psychological stress were investigated. To this aim in vitro models were used to simulate the spaceflight environment and collect data of altered wound healing and fibroblast morphology. The wound healing ability of NHDF cells, investigated through a scratch assay, seemed not significantly affected by space stressors, which is in contrast with earlier experiments performed at SCK CEN. Cytoskeleton rearrangement upon exposure to stress, X-irradiation and simulated microgravity was further shown by immunostainings for -tubulin and F-actin filaments, suggestive for the presence of stress fibers. Moreover, significant individual, as well as interaction effects between the conditions were observed on filament intensities and spreading. Finally, Western blot analysis for extracellular matrix proteins collagen type I and type III was performed, to determine altered expression in NHDF cells exposed to space stressors, since they are crucial for proper wound healing. Here, stress reduced collagen type I expression in lysates, which is in contrast with the enhancing effect of X-irradiation. Contrary to collagen type I, no effect of space conditions could be observed in terms of collagen type III expression. From the thesis it is clear that individual space stressors and/or a combination thereof can affect normal skin cell behavior upon wounding. In particular, cytoskeleton reorganization and altered collagen type I expression was observed in exposed NHDF cells, both important for cell migration, adhesion and proper wound healing. It is important to further investigate and reveal potential interaction effects of the spaceflight environment on the skin of astronauts, and to learn more about the underlying mechanism of a disturbed wound healing. This will determine the impact on their health and improve their protection during future long-duration deep-space missions by investigating and applying possible countermeasures. Also on Earth, these understandings can contribute to find solutions for people who experience difficulties with proper wound healing, including patients with pressure sores or diabetics.