Co-culture cassette for anaerobes and primary human intestinal epithelium

厌氧菌和原代人肠上皮共培养盒

基本信息

批准号：
10018032
负责人：
Christopher Eldridge Sims
金额：
$ 74.57万
依托单位：
ALTIS BIOSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-21 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10018032
关键词：
3-Dimensional Academia Air Anaerobic Bacteria Area Awareness Biological Assay Biological Models Biological Sciences Biotechnology Cell Culture Techniques Cells Coculture Techniques Colon Complex Computer Models Devices Diet Disease Distant Environment Environmental Risk Factor Epithelial Epithelial Cells Epithelium Exposure to Food Foundations Funding Gastrointestinal tract structure Generations Genetic Genetic Engineering Goals Growth Health Human Human Biology Human body In Vitro Incubators Individual Industry Injections Intestines Intuition Investigation Legal patent Letters Link Metabolism Microbe Mission Modeling Names North Carolina Organ Organoids Oxygen Personal Satisfaction Pharmaceutical Preparations Pharmacologic Substance Phase Physiology Play Probiotics Recreation Reproducibility Research Role Scientist Small Business Innovation Research Grant Solid System Therapeutic Tissues Tumor Cell Line Universities Validation Work base biobank cell type colon bacteria demographics design dysbiosis gastrointestinal gastrointestinal system genetic makeup genome wide association study gut bacteria gut microbiome gut microbiota host microbiome host microbiota host-microbe interactions human stem cells improved in vitro Model in vivo innovation interest intestinal epithelium matrigel microbial microbiome microbiome research microbiota model design monolayer prebiotics programs prototype scale up screening stem cells tissue culture uptake

项目摘要

Project Summary The human colon is a remarkable organ, playing critical roles in drug uptake and metabolism as well as harboring the 100 trillion microbial cells of the microbiome, which itself has multiple impacts on human health. For these reasons, there is a widespread need in academia and the biotechnology marketplace for in vitro studies of human colon physiology and the interaction between colon tissue and the anaerobic bacteria of the microbiome. To meet this need, Altis Biosystems, Inc., an early stage biotechnology company, has collaborated with scientists at the University of North Carolina (UNC) at Chapel Hill to develop a new platform for cell culture to co-culture normal, human colonic epithelial cells with anaerobic microbiota, named the Self-sustaining Intestinal Microbiome Platform (SIMPle). SIMPle is an easy-to-use and intuitive platform to replicate the steep oxygen gradient across the in vivo colonic epithelium, thus create the appropriate environment required for anaerobes while maintaining viable, healthy epithelial tissue. We have finished the SBIR Phase I program by designing, prototyping, validating the SIMPLe that fits a standard 12-well plate (SIMPle12). The generation of a steep O2 gradient was confirmed, and its impact on cells was characterized. The co-culture of facultative anaerobes with human colonic epithelium in SIMPle12 platforms was validated. All proposed milestones in the Phase I SBIR were accomplished, thus providing a solid foundation for this Phase II SBIR application. The focus of this Phase II proposal is to scale up SIMPLe platform to a 96-well format (SIMPle96) to meet the market needs for screening assays. The SIMPle96 platform will be prototyped and validated, and human colonic epithelium and co-culture with obligate anaerobes will be characterized. Use SIMPle96 platform for screening probiotics will be demonstrated. An external validation of the platform will be performed to demonstrate its utility in microbe-intestinal assays. The SIMPle co-culture platforms are expected to revolutionize microbiome research by enabling the function of host-microbe interactions to be interrogated.

项目摘要人类结肠是一个非凡的器官，在药物摄取和代谢以及含有微生物组的100万亿微生物细胞，本身对人类健康有多种影响。由于这些原因，很普遍人类结肠生理体外研究的学术和生物技术市场以及结肠组织与微生物组的厌氧菌细菌之间的相互作用。见面早期生物技术公司Altis Biosystems，Inc。的这种需求已与北卡罗来纳大学（UNC）的科学家在教堂山开发一个新平台用于细胞培养以与厌氧菌群共培养正常的人类结肠上皮细胞，命名为自我维持的肠道微生物组平台（简单）。简单是易于使用的和直观的平台，以复制体内结肠上陡峭的氧气梯度上皮，因此在维护的同时创造了厌氧所需的适当环境可行的健康上皮组织。我们通过设计完成了SBIR I期计划原型制作，验证适合标准12孔板的简单（Simple12）。这一代确认了陡峭的O2梯度，并表征了其对细胞的影响。共培养在Simple12平台中与人类结肠上皮的兼性厌氧菌已得到验证。在I阶段SBIR中所有提议的里程碑均已完成，从而提供了固体此II阶段SBIR应用的基础。该第二阶段建议的重点是扩大规模简单的平台达到96孔格式（Simple96），以满足筛选分析的市场需求。 Simple96平台将进行原型和验证，人类结肠上皮和具有强大厌氧菌的共同文化将被表征。使用Simple96平台进行筛选将证明益生菌。平台的外部验证将进行证明其在微生物 - 肠验测定中的效用。简单的共培养平台是预计通过启用宿主微杆的功能来彻底改变微生物组研究相互作用要审问。