Adipokine-enriched brown adipocytes for treating polycystic ovary syndromes

富含脂肪因子的棕色脂肪细胞用于治疗多囊卵巢综合征

• 批准号: 10546546
• 负责人: Yongxing Liu
• 金额: $ 25.66万
• 依托单位: BIORESTORATIVE THERAPIES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546546
• 关键词: Acne; Address; Adipocytes; Adipose tissue; Affect; Age; Allogenic; Androgens; Animals; Anovulation; Biological Assay; Biological Markers; Brown Fat; Carcinoma; Cardiovascular Diseases; Caring; Cell Aging; Cell Transplantation; Cells; Clinical; Complex; Dermatologic; Devices; Encapsulated; Endocrine; Endocrine System Diseases; Estrus; Etiology; FGF21 gene; Familial Hypercholesterolemia; Female; Foreign-Body Reaction; Gene Expression; Gene Proteins; Genes; Genetic; Genetic Transcription; Gonadotropins; Health Care Costs; Hirsutism; Histopathology; Homeostasis; Hormonal; Hormone imbalance; Hormones; Human; Hyperandrogenism; Hyperinsulinism; Immune; Infertility; Insulin; Insulin Resistance; Life Style; Link; Literature; Mediating; Mental Depression; Metabolic; Metabolic Diseases; Metabolism; Modeling; Mus; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Ovarian; Ovarian Cysts; Ovarian aging; Overweight; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Phenotype; Polycystic Ovary Syndrome; Population; Protective Devices; Protein Secretion; Protocols documentation; Rattus; Regimen; Resistance; Risk; Safety; Selection Criteria; Sleep Apnea Syndromes; Small Business Innovation Research Grant; Symptoms; Testing; Testosterone; Therapeutic; Transplantation; United States; adipokines; adiponectin; base; clinically relevant; clinically significant; comorbidity; dehydroepiandrosterone; diabetes risk; hypothalamic pituitary ovarian axis; immunoregulation; improved; in vivo evaluation; metabolic phenotype; mouse model; novel therapeutics; obese patients; persistent symptom; prevent; primary endpoint; programs; protective effect; protein profiling; reduce symptoms; reproductive; secondary endpoint; standard of care; stem cell population; stem cells; subcutaneous; success

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.

摘要 多囊卵巢综合征(PCOS)影响6-18%的育龄女性，是最常见的 这一人群中的内分泌疾病。多囊卵巢综合征会导致妇科、皮肤病和新陈代谢的并存， 还会增加患2型糖尿病(T2D)、心血管疾病(CVD)和 精神问题，包括严重的抑郁症。多囊卵巢综合征与复杂的激素失调有关，如 高雄激素血症、高胰岛素血症和促性腺激素失调。多囊卵巢综合征通常与 代谢紊乱，50%-70%的PCOS患者表现出胰岛素抵抗，10%的T2D患者，这意味着 它们之间潜在的因果联系。目前的护理标准包括生活方式的改变和多重 一系列旨在缓解症状的药物。药物治疗通常成功率适中，而且有 对T2D、心血管疾病和精神问题的长期风险影响有限。我们建议使用新陈代谢活性 棕色脂肪细胞，它具有高分泌内分泌因子，包括但不限于脂联素，以治疗 多囊卵巢综合征。其作用机制可能与棕色的代谢活动和内分泌分泌有关。 脂肪细胞，以前在代谢程序中被广泛研究，现在表明临床益处 对于多囊卵巢综合征的治疗也是如此。目前的第一阶段SBIR项目旨在基于我们的银行来检验假设 目前包含来自捐赠者的150+细胞群，并评估所选的临床相关疗效 在已建立的小鼠模型中进行细胞移植。