A 2D Intestinal Crypt Platform for Compound Screens

用于复合屏幕的 2D 肠隐窝平台

• 批准号: 10708947
• 负责人: Christopher Eldridge Sims
• 金额: $ 90.03万
• 依托单位: ALTIS BIOSYSTEMS, INC.
• 依托单位国家: 美国
• 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/10708947
• 关键词: Acceleration; Age; Animal Model; Animals; Benchmarking; Biological Models; Biological Testing; Biotechnology; Cell Differentiation process; Cell Line; Cells; Cellular Structures; Characteristics; Child; Clinical Research; Collaborations; Colon; Diabetes Mellitus; Engineered Gene; Enterocytes; Enteroendocrine Cell; Environmental Impact; Epithelium; Foundations; Funding; Gender; Genetic Variation; Goals; Goblet Cells; Health; Heart; Human; Human Biology; Image Cytometry; In Vitro; Inflammation; Intestines; Liver; Lung; Malignant Neoplasms; Medicine; 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; 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; manufacturing test; microbial products; microphysiology system; monolayer; neoplastic cell; novel; organ on a chip; patient population; performance tests; pilot test; prebiotics; precision medicine; predictive test; prototype; screening; self-renewal; stem; stem cell differentiation; stem cell niche; stem cells; technology platform; two-dimensional

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

项目概要 肠上皮是体内分裂速度最快的组织，细胞的健康状况可以 因此，这个器官系统很容易受到环境毒素和药物的影响。 药物化合物、益生元和微生物产品的生物测试目标。 可以精确预测这些影响的肠道模型将减轻测试负担 减少对动物模型的依赖，最大限度地减少重叠评估的数量 为了帮助消除不必要的测试，Altis Biosystems Inc. 处于早期阶段。 生物技术公司将与华盛顿大学的科学家合作开发 一种模拟人类原代肠道上皮的新型二维 (2D) 隐窝平台。 肠上皮干细胞将在平台上进行图案化以模仿肠道上皮 这种平面二维细胞具有干细胞生态位以及迁移性增殖和分化细胞。 平台将以坚固且可重复的方式实现高内涵/高通量测定。 在第二阶段 SBIR 中，这种合作将产生一个商业 2D 隐窝器官芯片平台 使用已建立的 12 孔板并扩展平台以纳入 96 孔板高含量 此外，该商业平台将与阿斯利康合作进行基准测试。 肿瘤学安全团队作为肠道脱靶效应的预测分析系统