Development of a microphysiologic system to assay the interaction of the human colonic epithelium on Clostridium difficile

开发微生理系统来测定人结肠上皮对艰难梭菌的相互作用

基本信息

批准号：
10539253
负责人：
Nancy L. Allbritton
金额：
$ 54.01万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10539253
关键词：
3-Dimensional Address Adverse event Anaerobic Bacteria Animal Model Animals Antibiotics Area Bacillus Bacteria Behavior Biological Assay Cecum Cell Communication Cell Compartmentation Cell Culture Techniques Cell Differentiation process Cell physiology Cells Centers for Disease Control and Prevention (U.S.)Cessation of life Clindamycin Clinical Clostridium difficile Coculture Techniques Colon Data Development Diarrhea Disease Engineering Environment Epithelial Cells Epithelium Event Exhibits Future Gastrointestinal tract structure Germination Goals Growth Hamsters Human Human Microbiome Immune response In Vitro Incidence Individual Infection Infectious Agent Interdisciplinary Study Intestines Invaded Investigation Large Intestine Mammalian Cell Mediating Methods Microbe Modeling Molecular Morbidity - disease rate Mucous body substance Mus Organoids Pathogenicity Patients Perforation Physiological Prevention Process Production Proliferating Race Recurrence Reproduction spores Research Project Grants Resistance Risk Sampling Screening procedure Sepsis Source System Techniques Technology Testing Time Tissues Toxic Megacolon Toxin Tumor Cell Line Vancomycin Work base cell type clinically relevant cost estimate design diarrheal disease experimental study fecal transplantation health care settings human adult stem cell human disease human model human old age (65+)improved innovation interest intestinal epithelium matrigel microbial microbiome microbiome alteration microbiota microphysiology system mortality novel organ on a chip pathogen pathogenic microbe response sex stem cells technology platform

项目摘要

Project Summary In the current application, a collaborative, multidisciplinary research project is proposed to develop and validate an innovative platform to study the interactions between primary human intestinal cells and the pathogenic microbe, Clostridium difficile (C. difficile). A new and uniquely engineered technology will create an intestine-on-chip (organ-on-chip) platform capable of maintaining a viable human colonic epithelium co-cultured with luminal nonpathogenic and pathogenic obligate anaerobes in order to study fundamental cellular processes that occur during the interaction between the human and microbial cells. The work will design, model and engineer a three-dimensional intestinal-cell culture platform that supports a physiologic mucous layer as well as mimics the sheer forces of the passage of fecal material. The design of this system will make it possible to observe and perturb the human-microbe cell-cell interactions and modify respective environments to elucidate the underlying cellular and molecular events key to these interactions. A powerful attribute of the proposal is that these experiments will leverage new stem-cell culture methods that produce a normal, primary human colonic epithelium rather than use tumor cell lines as the source of the mammalian cells. The experimental data generated by the proposed microphysiological system will in the future provide key information concerning prevention and treatment option(s) for C. difficile as well as provide a new technique for the study of other infectious organisms involving the gastrointestinal tract.

项目概要在当前的申请中，提出了一个协作的、多学科的研究项目开发并验证一个创新平台来研究原始人类之间的相互作用肠道细胞和病原微生物艰难梭菌（C. difficile）。一个新颖且独特的工程技术将创建一个肠芯片（器官芯片）平台，能够维持与腔内非致病性和共培养的存活的人类结肠上皮致病性专性厌氧菌，以研究发生的基本细胞过程在人类和微生物细胞相互作用的过程中。这项工作将设计、建模和设计一个支持生理学的三维肠道细胞培养平台粘液层并模仿粪便物质通过的纯粹力量。的设计该系统将使观察和扰动人类微生物细胞细胞成为可能相互作用并修改各自的环境以阐明潜在的细胞和分子事件是这些相互作用的关键。该提案的一个强大属性是，这些实验将利用新的干细胞培养方法来产生正常的、原代的人结肠上皮而不是使用肿瘤细胞系作为哺乳动物细胞的来源。所提出的微生理系统生成的实验数据将在未来提供有关艰难梭菌预防和治疗方案的关键信息以及为研究其他感染性生物体提供了一种新技术胃肠道。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Human 2D Crypt Model for Assaying Intestinal Stem Cell Proliferation and Differentiation.

DOI：
10.1021/acs.analchem.2c00905
发表时间：
2022-07-05
期刊：
ANALYTICAL CHEMISTRY
影响因子：
7.4
作者：
Wang, Yuli;Sims, Christopher E.;Allbritton, Nancy L.
通讯作者：
Allbritton, Nancy L.

Development of a Primary Human Intestinal Epithelium Enriched in L-Cells for Assay of GLP-1 Secretion.

DOI：
10.1021/acs.analchem.2c00912
发表时间：
2022-07-12
期刊：
ANALYTICAL CHEMISTRY
影响因子：
7.4
作者：
Villegas-Novoa, Cecilia;Wang, Yuli;Sims, Christopher E.;Allbritton, Nancy L.
通讯作者：
Allbritton, Nancy L.

Suspended Collagen Hydrogels to Replicate Human Colonic Epithelial Cell Interactions with Immune Cells.

DOI：
10.1002/adbi.202200129
发表时间：
2022-11
期刊：
ADVANCED BIOLOGY
影响因子：
3.7
作者：
Hinman, Samuel S.;Massaro, Angelo;Wang, Yuli;Sims, Christopher E.;Kim, Raehyun;Allbritton, Nancy L.
通讯作者：
Allbritton, Nancy L.