Adipokine-enriched brown adipocytes for treating polycystic ovary syndromes

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Abstract Polycystic ovary syndromes (PCOS) affect 6-18% of reproductive age female, representing the most common endocrine disease in this population. PCOS causes gynecological, dermatologic and metabolic comorbidities, and also imposes long-term risks of diabetes mellitus type 2 (T2D), cardiovascular diseases (CVD) and psychiatric problems including severe depression. PCOS is related to complex hormonal dysregulations such as hyperandrogenism, hyperinsulinemia and gonadotropin dysregulation. And PCOS is commonly associated with metabolic disorders, with 50-70% of PCOS patients showing insulin resistance and 10% with T2D, implying a potential causative interlinks between them. Current standard of care includes life style changes and multiple lines of medications with aims to relieve symptoms. Medications usually have moderate success rates, and have limited effects on long-term risks of T2D, CVD and psychiatric problems. We propose to use metabolically active brown adipocytes, which have high secretion of endocrine factors including but not limited to adiponectin, to treat PCOS. The working mechanisms may involve the both metabolic activities and endocrine secretions of brown adipocytes, which are previously extensively studied in metabolic programs and now indicative of clinical benefit for PCOS treatment as well. The present Phase I SBIR project aims to test the hypothesis based on our bank currently containing 150+ cell populations from donor, and evaluate clinically relevant efficacy of the selected cells in an established mouse model.