A 2D Intestinal Crypt Platform for Compound Screens

项目总结 肠道上皮是人体内分裂最快的组织，细胞的健康状况可以 容易受到环境毒素和药物的影响。因此，这个器官系统是一种质数 药用化合物、益生元和微生物产品的生物测试目标。An In 能够准确预测这些影响的体外肠道模型将通过以下方式减轻测试负担 减少对动物模型的依赖，最大限度地减少重叠评估的数量 帮助消除不必要的测试。为了满足这一需求，Altis BiosSystems Inc. 生物技术公司，将与华盛顿大学的科学家合作开发 一种新的二维(2D)隐窝平台，模拟肠道上皮。人类原始性 肠上皮干细胞将在平台上形成图案，以模拟肠上皮 具有干细胞利基，具有迁移性增殖和分化细胞。此平面2D 平台将以坚固和可重复的方式实现高含量/高通量分析。 在这个第二阶段的SBIR中，这一合作将产生一个商业2D加密芯片器官平台 利用已建立的12孔板并扩展平台，纳入96孔板的高含量 格式化。此外，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

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