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

补充项目总结

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.