Human Sertoli Cell Model for Study of Male Reproductive Function and Toxicity

用于研究男性生殖功能和毒性的人类支持细胞模型

• 批准号: 7327186
• 负责人: Constance M John
• 金额: $ 25.52万
• 依托单位: MANDALMED, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-14 至 2009-01-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7327186
• 关键词: Accounting; Affect; Animals; Anti-Infective Agents; Antimalarials; Architecture; Area; Biological Assay; Biological Models; Blood - brain barrier anatomy; Blood-Testis Barrier; Cadmium chloride; Cell Death; Cell Polarity; Cell model; Cell physiology; Cells; Chemicals; Cisplatin; Coculture Techniques; Complex; Conditioned Culture Media; Data; Detection; Disruption; Dose; Drug Delivery Systems; Drug Efflux; Drug Industry; Electrical Resistance; Evaluation; Flow Cytometry; Follicle Stimulating Hormone; Freezing; Future; Generations; Genetic; Genitourinary system; Goals; HIV; HIV Protease Inhibitors; Harvest; High Pressure Liquid Chromatography; Human; Immunoblotting; Immunosuppressive Agents; In Vitro; Indinavir; Infertility; Knowledge; Legal patent; Male Contraceptive Agents; Male Genital Organs; Malignant neoplasm of testis; Marketing; Measurement; Mefloquine; Membrane; Methodology; Methods; Modeling; Mono-S; Movement; Permeability; Pesticides; Pharmaceutical Preparations; Phase; Poison; Polychlorinated Biphenyls; Population; Proliferating; Proteins; Proteomics; Relative (related person); Reproduction; Reproductive Health; Research; Saquinavir; Scientist; Screening procedure; Seminal fluid; Spermatogenesis; Standardization; Study models; Supplementation; System; Testing; Testis; Testosterone; Thinking; Tight Junctions; Time; Tissue Donors; Tissues; Toxic effect; Toxicology; Transferrin; chemotherapeutic agent; cost; density; drug distribution; environmental chemical; extracellular; immunoregulation; inhibitor/antagonist; male; mono-(2-ethylhexyl)phthalate; novel; phthalate; phthalates; reproductive; reproductive function; research and development; response; sertoli cell; spermatogenic epithelium structure; three-dimensional modeling; toxicant

DESCRIPTION (provided by applicant): The overall goal of the Phase I research is to develop a three-dimensional model of the blood-testis barrier (BTB) consisting of primary human Sertoli cells cultured on permeable membrane supports. The human Sertoli cells have been isolated from normal human testis tissue by MandalMed scientists using a novel patent-pending methodology. To our knowledge, due to difficulty in their isolation human Sertoli cells have never been readily available before for in vitro studies. Applications of the product include studies of the distribution and toxicology of drugs and industrial chemicals, infertility research, development of male contraceptive agents, and eventually for creation of a model of human spermatogenesis. There is a great need for more accurate, less costly and time- consuming methods of assessing effects on drug distribution in the testis, reproductive function and toxicity. Three Specific Aims have been identified for the Phase I research as described below. I. Develop a transwell three-dimensional culture system for primary human Sertoli cells as a model of the blood-testis barrier (BTB). II. Assess the ability of model compounds to affect permeability of the model BTB. III. Assess the toxicity of compounds for the model BTB. Areas of focus that are envisioned for Phase II are identification of genetic or proteomic markers for human Sertoli cell function, including the formation or disruption of junctions, transporters, immunomodulation, comparisons with animal studies of distribution of drugs for the testis, male reproductive toxicity, and the standardization as a method for quantifying human BTB permeability and Sertoli cell toxicity. In Phase II we will develop more complex, multicellular model systems. The overall goal of the Phase I research is to develop a three-dimensional model of the blood-testis barrier (BTB) consisting of primary human Sertoli cells cultured on permeable membrane supports. Applications of the product include studies of the distribution and toxicology of drugs and industrial chemicals, infertility research, development of male contraceptive agents, and eventually for creation of a model of human spermatogenesis. There is a great need for more accurate, less costly and time- consuming methods of assessing effects on reproductive function and toxicity.

描述(申请人提供)：第一阶段研究的总体目标是开发一个血-睾丸屏障(BTB)的三维模型，该模型由培养在可渗透膜支架上的原代人类支持细胞组成。MandalMed科学家使用一种正在申请专利的新方法从正常人类睾丸组织中分离出人类Sertoli细胞。据我们所知，由于分离困难，人类Sertoli细胞以前从未容易地用于体外研究。该产品的应用包括药物和工业化学品的分布和毒理学研究、不育症研究、男性避孕药的开发，以及最终创建人类精子发生的模型。迫切需要更准确、成本更低、耗时更长的方法来评估药物在睾丸中的分布、生殖功能和毒性。已经为第一阶段研究确定了三个具体目标，如下所述。I.建立原代人类支持细胞的Transwell三维培养系统，作为血-睾丸屏障(BTB)的模型。评估模型化合物对模型BTB渗透性的影响能力。评估化合物对模型BTB的毒性。预计第二阶段的重点领域是识别人类支持细胞功能的遗传或蛋白质组标记，包括连接、转运蛋白、免疫调节的形成或破坏，与动物研究的比较，睾丸药物的分布，男性生殖毒性，以及作为量化人类BTB通透性和支持细胞毒性的方法的标准化。在第二阶段，我们将开发更复杂的多细胞模型系统。第一阶段研究的总体目标是开发一个血-睾丸屏障(BTB)的三维模型，该模型由原代培养在可渗透膜支架上的人类Sertoli细胞组成。该产品的应用包括药物和工业化学品的分布和毒理学研究、不育症研究、男性避孕药的开发，以及最终创建人类精子发生的模型。迫切需要更准确、成本更低、耗时更长的方法来评估对生殖功能和毒性的影响。