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

器官芯片作为研究空间对人类肠道生理学影响的平台：上皮粘膜与感觉神经元和微生物组的相互作用

• 批准号: 9789393
• 负责人: Christopher D. Hinojosa
• 金额: $ 61.06万
• 依托单位: EMULATE, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789393
• 关键词: Afferent Neurons; Architecture; Award; Bacteria; Bacterial Infections; Basic Science; Biological Assay; Calcium; Cell physiology; Cells; Cellular Morphology; ChIP-on-chip; Clinical; Communities; Detection; Development; Disease; Drug Industry; Ecosystem; Enteral; Environment; Epidemic; Epithelial; Epithelial Cells; Exposure to; Expression Profiling; Fluorescent Dyes; Foundations; Gastrointestinal Diseases; Gene Expression; Government Agencies; Grant; Health; Human; Image; Immune; Immune response; Impact evaluation; In Vitro; Industry; Infection; Institutes; International; Intervention; Intestines; Lactobacillus; Lamina Propria; Liquid substance; Maintenance; Massachusetts; Measures; Mechanics; Microgravity; Microscope; Microscopy; Modeling; Molecular; Morphology; Mucous Membrane; Neurons; Organ; Pathogenicity; Peristalsis; Permeability; Physiology; Planet Earth; Prevention; Privatization; Probiotics; Prophylactic treatment; Request for Applications; Salmonella typhimurium; Science; Sensory; Space Flight; Stimulus; Stretching; Structure; System; Targeted Research; Technology; Time; Tissues; Translational Research; United States National Aeronautics and Space Administration; United States National Institutes of Health; Universities; Work; antimicrobial; base; cell motility; cell type; clinically relevant; drug development; experimental study; foodborne; foodborne pathogen; host microbiome; human model; immunoregulation; in vivo; induced pluripotent stem cell; insight; microbiome; microphysiology system; nerve supply; novel; pathogenic bacteria; real-time images; response; space station; stressor; treatment response

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.

摘要 美国国立卫生研究院（NIH）、太空科学促进中心（CASIS）、 用于应用（RFA），-靶向研究（TR），18-001，我们提出应用Emulate Inc.的器官芯片技术， 评估空间飞行对人体器官的体外影响。Emulate是一家新兴的科技初创企业 是在马萨诸塞州剑桥的哈佛大学的韦氏研究所开发的。建议的工作重点是增加 将实时成像功能添加到已与实施合作伙伴一起开发的空间自动化硬件中 SpaceTango通过RFA-TR-16-019授予的赠款。该系统将使人体实验， 相关的微生理学系统，以了解微重力和空间飞行造成的 压力因素对人体生理、疾病发展和对干预措施的反应的影响。我们计划进一步展示 通过将其应用于研究包括结肠的人类神经支配肠芯片（hiIC）， 上皮细胞、固有层衍生的驻留免疫细胞、肠感觉神经元和微生物组。研究将 研究这种新模型对致病菌的免疫应答， 细菌将在地球和国际空间站上对相同的硬件进行研究，并提供新的 深入了解空间环境对免疫反应的影响。新的成像功能将允许 实时成像的器官芯片在整个太空旅程和感染病原菌，给一个 这是一个前所未有的视角，展示了系统如何在这种独特的环境中做出反应。成功实施我们的空间 兼容的硬件，并将其应用扩展到我们的新型hiIC芯片，将显示出体内相关的价值， 科学界可用于评价微重力对生理学影响的体外平台 和许多人体器官的疾病，并以新颖的、临床相关的方式支持药物开发。