Organ-Chips as a Platform for Studying Effects of Space on Human Enteric Physiology: Interactions of Epithelial Mucosa with Sensory Neurons and Microbiome

摘要 应美国国立卫生研究院--空间科学促进中心--的要求 对于应用程序(RFA)，目标研究(TR)，18-001我们建议应用EMULATE Inc.的器官芯片技术， 目的：评估太空飞行对人体器官的影响。Eulate是一家基于技术的新成立的初创企业 由马萨诸塞州剑桥市哈佛大学的怀斯研究所开发。拟议的工作重点是添加 为已经与实施合作伙伴开发的空间自动化硬件提供实时映像功能 SpaceTango通过RFA-TR-16-019授予的赠款。该系统将使人体、活体实验成为可能。 理解微重力和其他空间飞行影响的相关微生理系统 人类生理、疾病发展和对干预措施的反应的压力源。我们计划进一步展示 该自动化平台在人神经肠道芯片(HiIC)研究中的应用价值 上皮细胞、固有层衍生的常驻免疫细胞、肠道感觉神经元和微生物组。研究将会 研究这一新模型在加入和不加入益生菌的情况下对致病菌的免疫应答。 细菌。将在地球和国际空间站上进行相同硬件的研究，并提供新的 洞察空间环境对免疫反应的影响。新的成像功能将允许 对器官芯片整个太空旅程和感染病原体的实时成像，给出了一个 史无前例地了解系统在这一独特环境中的反应。成功实施我们的太空计划 兼容的硬件，并将其应用扩展到我们的新型HIC芯片，将展示体内相关的价值，在 可供科学界用于评估微重力对生理学影响的体外平台 并以新的、临床相关的方式支持药物开发。

Abstract In response to the National Institutes of Health (NIH), -Center for the Advancement of Science in Space (CASIS), -Request for 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 technology developed at the Wyss Institute at Harvard University in Cambridge, Massachusetts. The proposed work focuses on adding live imaging functionality to the automated hardware for space already being developed with Implementation Partners SpaceTango through the grant awarded from RFA-TR-16-019. This system will enable experiments in human, in vivo relevant microphysiological systems for understanding of the impact of microgravity and other space flight-imposed stressors on human physiology, disease development and response to interventions. We plan to further demonstrate the value of this automated platform by applying it to study a human innervated Intestine-Chip (hiIC) which includes colonic epithelial cells, lamina propria derived resident immune cells, enteric sensory neurons, and microbiome. Studies will investigate the immune response of this novel model to pathogenic bacteria with and without the incorporation of probiotic bacteria. Studies on identical hardware will be conducted on earth and on the International Space Station, and provide new insights into the influence of the space environment on immune response. The new imaging functionality will allow for real-time imaging of the organ-chips throughout their space journey and infection with pathogenic bacteria, giving an unprecedented view of how the system responds in this unique environment. Successful implementation of our space compatible hardware, and extending its application to our novel hiIC-chip, will show the value of an in vivo relevant, in vitro platform that can be utilized by the scientific community for the evaluation of the impact of microgravity in physiology and disease of a number of human organs, and support drug development in novel, clinically relevant ways.