3D Intestinal Tissues

核心B-摘要 核心B将利用为3D肠道系统开发的改进来支持准备和 组织模型的实用性，包括为所有项目生成支架和种子支架/组织。这个 计划基于我们广泛的初步数据，我们已经在结构和功能上证明了这些数据- 相关的3D人体肠道组织用于传染病的研究。肠道系统包括 肠样原代细胞来源--一种具有几何工程中空的三维多孔蛋白质支架系统 对大肠和小肠组织都有适应性的管腔。在目标1中，重点将放在准备上 三个研究项目的支架和3D肠道系统。这里的目标是提供肠道 组织支持三个研究项目(每周60个系统)，从 临床，建立来自小肠和结肠的早期传代有机物质，并训练 各个项目中的个人。此外，重点将是记录所有材料以进行验证和 质量控制，以确保重现性。在目标2中，重点将放在3D肠道组织的优化上。 这里的目标是继续优化目前开发的3D人体肠道组织，这些组织由 与生理相关的有机化合物，并发展出越来越复杂的特征，以便于分析 肠道病原体。这些活动将包括加入更多的细胞类型，补充 具有ECM组件的支架，以及进一步开发用于控制流动、蠕动的生物反应器系统 以及氧气水平。一个由教员、博士后研究员和一名技术人员组成的团队将支持核心B的需求 并在计划的所有阶段与研究团队密切合作。

Core B – Summary Core B will utilize the improvements developed for the 3D intestinal systems to support the preparation and utility of the tissue models, including generating the scaffolds and seeded scaffolds/tissues for all projects. The plans are based on our extensive preliminary data where we have demonstrated structurally- and functionally- relevant 3D human intestinal tissues for the study of infectious diseases. The intestinal systems include enteroid primary cell sources, a 3D porous protein scaffolding system with a geometrically-engineered hollow lumen with adaptability to both large and small intestinal tissues. In Aim #1 the focus will be on the preparation of scaffolds and 3D intestinal systems for the three research projects. Here the goal is to provide intestinal tissues to support the three research projects (60 systems per week), obtain primary tissue samples from the clinic, establish early passage organoid material from both the small intestine and the colon, and train individuals in the various projects. In addition, a focus will be on documenting all materials for validation and quality control to assure reproducibility. In Aim #2 the focus will be on optimization of the 3D intestinal tissues. Here the goal is to continue to optimize the currently developed 3D human intestinal tissues generated from organoids for physiological relevance, and develop increasingly complex features to facilitate analysis of intestinal pathogens. These activities will include the incorporation of additional cell types, supplementation of the scaffolds with ECM components, and further development of a bioreactor system to control flow, peristalsis and oxygen levels. A team of faculty, post doctoral fellows and a technician will support the needs of Core B and work closely with the research teams on all phases of the plans.