Space medicine: use of ex vivo human respiratory mucosa in the survey of the effects of microgravity on the respiratory system

Abstract

In the near future, the length and scope of space travel is set to increase significantly. The number of individuals who will have access to extra-terrestrial travels is also increasing. In view of the growing international interest towards manned long-term space exploration, possible effects of exposure to microgravity conditions affecting the respiratory system are subject of interest by major space agencies (NASA and ESA primarily). Our team has developed an advanced 3d tissue model of the human bronchial mucosa within a wide research project involving several universities and space agencies at international level. The model will be used to study the structural/functional alterations of the bronchial mucosa that may arise from prolonged exposure to reduced gravity conditions. Among the different modifications to be evaluated: development and performance of the pulmonary barrier; possible ciliogenesis modification due to its effects on fluid mechanics and mechanotransduction; formation of multi-cellular structures (Cell-Cell and ECM-Cell Interactions). The design and realization of experiments aboard the International Space Station (ISS) often clashes with greater difficulties than at ground level. Our work was to check the resilience of the model to the prohibitive environmental conditions present on board the vectors that transport the samples to the ISS, and to adapt the model to engineering requirements for proper functionality within the BIOLAB of ISS itself. To verify this, cell cultures were subjected to various boundary conditions: temperatures lower than growth optimum, reduced concentrations of CO2, restriction of gas exchange, prolonged starvation and storage of the culture medium at high temperatures. The bronchial mucosa cultures were analysed at the end of the treatments and their morphology was evaluated. We also used the monitoring of the Trans Epithelial Electric Resistance to evaluate the state of health of the cultures. The data obtained demonstrated how this culture model is able to overcome the critical phases of the journey to ISS and how it can conform to restrictive engineering requirements. It is possible to assert that in addition to the accurate reproduction of the bronchial human mucosa, the cell culture model possesses the characteristics necessary to be used in studies in an extreme environment such as the ISS, being able to provide data that could be relevant for future manned spaceflights.