Isolation and in vitro maintenance of intact colonic crypts from normal human col

正常人结肠完整结肠隐窝的分离和体外维持

• 批准号: 8737539
• 负责人: JAMES VARANI
• 金额: $ 20.29万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8737539
• 关键词: Adenomatous Polyps; Animal Model; Anoikis; Apoptosis; Biochemical; Biopsy; Cancerous; Cell Culture Techniques; Cell Line; Cell physiology; Cells; Chemopreventive Agent; Colon; Colon Carcinoma; Colonic Adenoma; Colonic Neoplasms; Defect; Development; Epithelium; Event; Extracellular Matrix; Goals; Growth; Growth Factor; Histologic; Human; In Vitro; Individual; Laboratories; Lesion; Maintenance; Malignant Neoplasms; Methods; Modeling; Molecular; Normal Cell; Normal tissue morphology; Organ Culture Techniques; Organoids; Phenotype; Polyps; Premalignant; Prevention; Process; Regulation; Research; Research Personnel; Rodent; Rodent Model; Sampling; Signal Pathway; Staging; Stem cells; Structure; System; Technology; Testing; Time; Tissue Expansion; Tissues; Tumor Cell Line; Undifferentiated; Xenograft procedure; abstracting; adenoma; anticancer research; base; cancer initiation; colonic crypt; in vivo; novel; pre-clinical; public health relevance; research study; success

DESCRIPTION (provided by applicant): Abstract the long-term goal of the research proposed here is to develop methods for the isolation and in vitro maintenance of intact colonic crypts from histologically normal human colon tissue and from adenomatous polyps / malignant tumors. The isolated colonic crypts maintained in culture will provide a unique culture system for examining the effects of potential chemopreventive agents in a preclinical setting as well as for examining various aspects of growth regulation in the colon. The same culture system will, hopefully, prove useful for isolation and characterization of stem cells from normal and aberrant crypts. To achieve the goals of this proposal, we will do the following: Specific Aim: Isolate crypts from histologically normal human colon tissue and from adenomatous polyps; develop culture conditions that maintain crypt histological structure and biochemical function and that allow for progression of the histologically-normal crypts through proliferation, differentiation an apoptosis in a spatially and temporally appropriate manner, while allowing for continued growth and expansion of the tissue derived from premalignant adenomatous polyps.

描述（由申请人提供）：摘要本文提出的研究的长期目标是开发从组织学正常的人类结肠组织和腺瘤性息肉/恶性肿瘤中分离和体外维持完整结肠隐窝的方法。保持在培养物中的分离的结肠隐窝将提供独特的培养系统，用于检查临床前环境中潜在化学预防剂的作用以及检查结肠中生长调节的各个方面。希望相同的培养系统可用于从正常和异常隐窝中分离和表征干细胞。为了实现该提案的目标，我们将做以下工作： 具体目标：从组织学正常的人类结肠组织和腺瘤性息肉中分离隐窝；开发维持隐窝组织学结构和生化功能的培养条件，并允许组织学正常的隐窝以空间和时间适当的方式通过增殖、分化和凋亡进行进展，同时允许源自癌前腺瘤息肉的组织持续生长和扩张。