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

补充项目摘要 多囊卵巢综合征是一种异质性内分泌疾病，影响5%至15%的 育龄妇女，并呈现出广泛的表型。它的典型特征是 高雄激素血症和无排卵性不孕症或多囊卵巢的形态特征，但也包括 代谢异常和其他几种健康并发症，如2型糖尿病，心血管疾病， 子宫内膜癌和卵巢癌。其病因是多因素的，包括环境、遗传和生活方式。 各种因素和目前的治疗策略仍然不能令人满意。研究这种病理很复杂。 此外，由于动物和体外多囊卵巢综合征模型的局限性，无法完全复制人类 生理学。此外，由于许多内分泌干扰物(EDCs)与病理生理学有关 在几种疾病中，一种系统可以测试不同浓度的多个内分泌细胞的组合，这表明 典型的人类暴露是必要的。我们目前的研究工作是部署一种动态微流控 平台，称为晶格，由外植体和组织工程器官的集成网络组成 与PCOS病理生理相关的模型，包括卵巢、肝脏、胰腺、脂肪、子宫内膜、输卵管、 还有乳房。鉴于Lattice的多功能性，该平台可用于研究任何微生理系统，如 正常的和病态的环境。在一个平板上可以研究多达8个不同的器官系统。本副刊 将能够将有关格子及其能力的数据存放到更广泛的MPS数据库中。这个独一无二的 多功能技术是研究和药物友好的，并将改变进行体外研究的方式 了解系统生物学，并在一个包含系统基本器官系统的平台上测试化合物 身体。

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.