PCOS and androgen-related disease modeling and drug testing in Multi-organ Integrated Microfluidic Reproductive Platform

多器官集成微流控生殖平台中的 PCOS 和雄激素相关疾病建模和药物测试

• 批准号: 10432418
• 负责人: Ji-Yong Julie Kim
• 金额: $ 8万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10432418
• 关键词: Affect; Androgens; Animals; Breast; Cardiovascular Diseases; Cells; Complex; Databases; Disease; Disease model; Endocrine Disruptors; Endocrine System Diseases; Endometrial Carcinoma; Endometrium; Etiology; Fatty acid glycerol esters; Functional disorder; Genetic; Goals; Health; Human; Hyperandrogenism; In Vitro; Infertility; Liver; Malignant neoplasm of ovary; Mammalian Oviducts; Metabolic; Microfluidics; Modeling; Morphology; Non-Insulin-Dependent Diabetes Mellitus; Organ; Organ Model; Ovarian; Ovary; Pancreas; Pathology; Phenotype; Physiology; Polycystic Ovary Syndrome; Research; System; Systems Biology; Technology; Testing; Therapeutic; Tissue Engineering; Woman; aged; body system; data submission; drug testing; exposed human population; lifestyle factors; microphysiology system; reproductive

Supplement Project Summary Polycystic ovary syndrome is a heterogeneous endocrine disorder affecting between 5 and 15% of reproductive aged women and presents with a wide spectrum of phenotypes. It is typically characterized by hyperandrogenism and anovulatory infertility or polycystic ovarian morphologic features but also includes metabolic abnormalities and several other health complications such as type 2 diabetes, cardiovascular disease, endometrial cancer, and ovarian cancer. Its etiology is multifactorial including environmental, genetic and lifestyle factors and current therapeutic strategies remain unsatisfactory. Studying this pathology is complicated further because of limitations in animal and in vitro PCOS models which are unable to fully replicate the human physiology. Moreover, since many endocrine disrupting chemicals (EDCs) are implicated in the pathophysiology of several diseases, a system that can test combinations of multiple EDCs at various concentrations, indicative of typical of human exposures, is needed. Our current research effort has been to deploy a dynamic microfluidic platform, called LATTICE, comprised of an integrated network of explants and of tissue-engineered organ models relevant to PCOS pathophysiology, including ovary, liver, pancreas, fat, endometrium, fallopian tube, and breast. Given the versatility of Lattice, this platform can be used to study any microphysiological system, in the normal and diseased contexts. Up to 8 different organ systems can be studied in one plate. This supplement will enable the deposition of data regarding Lattice and its abilities to the broader MPS database. This unique and versatile technology is research and pharma-friendly and will change the way in vitro studies are done to understand systems biology as well as test compounds in a platform that houses the essential organ systems of the body.

补充项目概要 多囊卵巢综合征是一种异质性内分泌疾病，影响 5% 至 15% 的女性 育龄妇女，并呈现出广泛的表型。其典型特点是 高雄激素血症和无排卵性不孕或多囊卵巢形态特征还包括 代谢异常和其他一些健康并发症，如 2 型糖尿病、心血管疾病、 子宫内膜癌、卵巢癌。其病因是多因素的，包括环境、遗传和生活方式 因素和目前的治疗策略仍然不能令人满意。研究这种病理学很复杂 进一步由于动物和体外 PCOS 模型的局限性，无法完全复制人类 生理。此外，由于许多内分泌干扰化学物质（EDC）与病理生理学有关 多种疾病的系统，可以测试不同浓度的多种 EDC 的组合，指示性 需要了解典型的人类暴露情况。我们目前的研究工作是部署动态微流体 称为 LATTICE 的平台，由外植体和组织工程器官的集成网络组成 与PCOS病理生理学相关的模型，包括卵巢、肝脏、胰腺、脂肪、子宫内膜、输卵管、 和乳房。鉴于 Lattice 的多功能性，该平台可用于研究任何微生理系统，例如 正常和患病环境。在一块板中最多可以研究 8 个不同的器官系统。本补充 将使有关莱迪思及其能力的数据沉积到更广泛的 MPS 数据库中。这种独特的 多功能技术对研究和药物友好，将改变体外研究的方式 了解系统生物学以及在容纳基本器官系统的平台中测试化合物 身体。