A 2D Intestinal Crypt Platform for Compound Screens

用于复合屏幕的 2D 肠隐窝平台

基本信息

批准号：
10611696
负责人：
Christopher Eldridge Sims
金额：
$ 98.84万
依托单位：
ALTIS BIOSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10611696
关键词：
Age Animal Model Animals Benchmarking Biological Models Biological Testing Biotechnology Cell Differentiation process Cell Line Cells Characteristics Child Clinical Research Collaborations Colon Diabetes Mellitus Engineered Gene Enterocytes Enteroendocrine Cell Epithelial Foundations Funding Gender Genetic Variation Goals Goblet Cells Health Heart Human Human Biology Image Cytometry In Vitro Inflammation Intestines Liver Lung Malignant Neoplasms Metabolism Minority Mission Modeling Oncology Oral Organ Organoids Pattern Performance Pharmaceutical Preparations Pharmacologic Substance Phase Physiology Preclinical Testing Proliferating Readiness Reproducibility Safety Scientist Screening procedure Small Business Innovation Research Grant Solid Source Structure System Techniques Technology Testing Tissue Differentiation Tissue Model Tissues Toxic Environmental Substances Toxic effect Toxicology Tumor Cell Line Universities Washington Woman Work adult stem cell base biobank body system cell immortalization cell type cognitive function commercial application commercialization cost effective drug development epithelial stem cell fetal gastrointestinal gastrointestinal epithelium high throughput screening high-throughput drug screening hormone regulation human disease human pluripotent stem cell human stem cells human tissue improved insight intestinal crypt intestinal epithelium microbial microphysiology system monolayer neoplastic cell novel organ on a chip patient population performance tests prebiotics precision medicine predictive test prototype screening self-renewal stem stem cell differentiation stem cell niche stem cells two-dimensional

项目摘要

PROJECT SUMMARY Intestinal epithelium is the fastest dividing tissue in the body, and the health of the cells can be easily impacted by environmental toxins and drugs. This organ system is therefore a prime target for biological testing of medicinal compounds, prebiotics, and microbial products. An in vitro gut model that can precisely predict these impacts will reduce the burden of testing by diminishing reliance on animal models, minimizing the number of overlapping assessments and helping to eliminate unnecessary testing. To meet this need, Altis Biosystems Inc., an early stage biotechnology company, will collaborate with scientists at University of Washington to develop a novel 2-dimensional (2D) crypt platform that emulates the gut epithelium. Human primary intestinal epithelial stem cells will be patterned on the platform to mimic a gut epithelium possessing a stem-cell niche, and migratory proliferating and differentiating cells. This planar 2D platform will enable high-content/high-throughput assays in a rugged and reproducible manner. In this Phase II SBIR, this collaboration will generate a commercial 2D crypts organ-on-a-chip platform using established 12-well plates and expand the platform to incorporate a 96-well plate high-content format. In addition, the commercial platform will be benchmarked in collaboration with AstraZeneca’s oncology safety team as a predictive assay system for intestinal off-target effects

项目摘要肠上皮是体内最快的分裂组织，细胞的健康可以很容易受到环境毒素和药物的影响。因此，这个器官系统是素数药物化合物，益生元和微生物产品的生物学测试靶标。一个可以准确预测这些影响的体外肠道模型将减少测试的燃烧减少对动物模型的依赖，最大程度地减少重叠评估的数量和有助于消除不必要的测试。为了满足这一需求，Altis Biosystems Inc.是早期阶段生物技术公司将与华盛顿大学的科学家合作开发一个新型的二维（2D）地穴平台，模拟肠道上皮。人类初选肠上皮干细胞将在平台上图案化，以模仿肠道上皮具有干细胞生态位，以及迁移的增殖和分化细胞。这个平面2d 平台将以崎and的繁殖方式实现高含量/高通量测定法。在此II阶段SBIR中，该合作将产生商业2D Crypts On-A-Chip平台使用已建立的12孔板并扩展平台以合并96孔板高音格式。此外，商业平台将与阿斯利康（Astrazeneca）合作进行基准测试肿瘤安全团队作为肠道脱靶效应的预测测定系统