ORGAN-CHIPS AS A PLATFORM FOR STUDYING EFFECTS OF SPACE ON HUMAN ENTERIC PHYSIOLOGY: INTERACTIONS OF EPITHELIAL MUCOSA WITH SENSORY NEURONS AND MICROBIOME

AbstractIn response to the National Institutes of Health (NIH), -Center for the Advancement of Science in Space (CASIS), -Requestfor Application (RFA), -Targeted Research (TR), 18-001 we propose to apply the Organ-Chip technology of Emulate Inc.,to assess the effects of space flight in human organs in vitro. Emulate is a newly founded start-up based on technologydeveloped at the Wyss Institute at Harvard University in Cambridge, Massachusetts. The proposed work focuses on addinglive imaging functionality to the automated hardware for space already being developed with Implementation PartnersSpaceTango through the grant awarded from RFA-TR-16-019. This system will enable experiments in human, in vivorelevant microphysiological systems for understanding of the impact of microgravity and other space flight-imposedstressors on human physiology, disease development and response to interventions. We plan to further demonstrate thevalue of this automated platform by applying it to study a human innervated Intestine-Chip (hiIC) which includes colonicepithelial cells, lamina propria derived resident immune cells, enteric sensory neurons, and microbiome. Studies willinvestigate the immune response of this novel model to pathogenic bacteria with and without the incorporation of probioticbacteria. Studies on identical hardware will be conducted on earth and on the International Space Station, and provide newinsights into the influence of the space environment on immune response. The new imaging functionality will allow forreal-time imaging of the organ-chips throughout their space journey and infection with pathogenic bacteria, giving anunprecedented view of how the system responds in this unique environment. Successful implementation of our spacecompatible hardware, and extending its application to our novel hiIC-chip, will show the value of an in vivo relevant, invitro platform that can be utilized by the scientific community for the evaluation of the impact of microgravity in physiologyand disease of a number of human organs, and support drug development in novel, clinically relevant ways.