Human Enteroid Core

人肠类核心

• 批准号: 8855933
• 负责人: NOAH Freeman SHROYER
• 金额: $ 15.06万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-15 至 2020-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8855933
• 关键词: 3-Dimensional; Animal Model; Apical; Biological Models; Categories; Cause of Death; Cell Line; Cells; Cessation of life; Child; Coculture Techniques; Colon; Conditioned Culture Media; Development; Disease; Duodenum; Endoscopic Biopsy; Engineering; Ensure; Enteral; Face; Freezing; Functional disorder; Genes; Goals; Growth; Growth Factor; Human; Immune; Immune system; Individual; Intestines; Measures; Mesenchymal; Mesenchyme; Modeling; Modification; Operative Surgical Procedures; Patients; Physiological; Physiology; Population; Pre-Clinical Model; Reagent; Reproducibility; Research Personnel; Research Project Grants; Sampling; Services; Severities; Small Intestines; Specimen; Surface; System; Technology Transfer; Testing; Tissues; Training; Validation; Villus; aged; cell type; cost effective; gastrointestinal epithelium; human disease; ileum; improved; intestinal epithelium; jejunum; meetings; member; microorganism; novel; novel strategies; pathogen; prevent; response; three-dimensional modeling

Project Summary – Core B Ex-vivo 3-D “mini-intestine” culture systems, termed enteroids, generated from human surgical specimens or endoscopic biopsies, have been found to recapitulate the multiple cell types that comprise the crypt-villus axis of the normal intestinal epithelium. The development of these enteroids has provided an exciting opportunity to advance our understanding of how pathogenic as well as beneficial microorganisms, many of which can prevent or lessen the severity of pathogen-induced diarrheal illness, interact with and induce responses from the intestinal epithelium. Therefore, the long range objectives of the Human Enteroid Core are to (1) characterize and compare human enteroids generated from three regions of the small intestine (duodenum, jejunum, ileum) and colon, from different patients to establish their use as models of human diarrheal diseases, (2) test new approaches to improve the enteroids as a relevant model of normal intestinal epithelium, and (3) to provide these enteroids and specialized growth reagents for use in the other projects (Core C, Projects 1, 2, and 3) proposed in this application. The goal of the Human Enteroid Core is to provide a centralized facility to meet the enteroid needs of all of the investigators involved in the NAMSED proposal. The specific functions of the Core will have two functions: a Service component, which will (1) Produce enteroid cultures from our existing bank for all projects (2) Establish enteroids from select new patient samples (3) Maintain frozen stocks of all enteroids (4) Passage and differentiate enteroids per requests (5) Maintain WNT, noggin, and r-spondin producing cells lines and standardized conditioned media for enteroid culture (6) Routinely test the enteroid lines for differentiation status (7) Technology transfer through training group members; a Development component, which will (1) Develop and standardize physiological measures as indicators of enteroid responses (2) Modify enteroids to enhance or deplete the presence of specific cell types or genes (3) Co-culture with mesenchymal cells to test for substitution of growth factors and develop novel structural components (e.g., inversion of the enteroids such that the apical surface faces outward) (4) Incorporate immune cells to improve the relevance of the enteroid model. The Core will be responsive to needs of the individual Projects, which may change as the research projects proceed, as the overall field evolves and as new platforms are engineered in Project 3. New activities will be developed to meet the needs of our and other NASMED project investigators. Our goal is complementary and collaborative in these exciting efforts to develop the enteroids as models to study enteric disease.

项目摘要 - 核心B 前体3-D“迷你智力”培养系统，称为肠toi，由人类手术产生 已经发现标本或内窥镜活检是为了概括多种细胞类型 这些的发展 Enteroids提供了一个令人兴奋的机会，以促进我们对致病性的理解 以及有益的微生物，其中许多都可以防止或减轻 病原体引起的腹泻病，与肠道的相互作用并影响反应 上皮。因此，人肠核的远距离对象是（1） 表征并比较了从小肠的三个区域产生的人类肠to （DuodeNum，Jejunum，Ileum）和结肠，来自不同的患者，以确立其用作模型 人类腹泻疾病，（2）测试新的方法以改善肠to虫作为相关的 正常肠上皮的模型，以及（3）提供这些肠to和专业生长的模型 在本应用程序中提出的其他项目（核心C，项目1、2和3）中使用的试剂。 人肠核的目的是提供集中的设施来满足肠托。 所有参与命名提案的调查人员的需求。特定功能 核心将具有两个功能：一个服务组件，该功能将（1）产生肠培养 来自我们现有银行的所有项目（2）从选定的新患者样品中建立肠to （3）维护所有肠toi的冷冻库存（4）通过 （5）维持Wnt，Noggin和R-Spondin产生细胞系和标准化条件 用于肠道培养的培养基（6）通常测试肠线以分化状态（7） 通过培训小组成员进行技术转移；开发组件，该组件将（1） 制定并标准化物理措施作为肠源性响应的指标（2）修改 用于增强或巧妙地存在特定细胞类型或基因（3）与共同培养 间充质细胞测试取代生长因子并发展新的结构 组件（例如，肠to骨的反转，使顶表面向外面）（4） 结合免疫细胞以改善肠托体模型的相关性。核心将是 响应各个项目的需求，这些项目可能会随着研究项目而改变 继续进行，随着整个领域的发展和新平台在项目3中进行了设计。 将开发活动以满足我们和其他NASMED项目调查人员的需求。 我们的目标是完整和协作的，以开发肠内 作为研究疾病的模型。