Ju Mingyan, Wang Zihan, Yang Weiwei, Sui Zhenhua, Wang Wenjing, Sun Kuikui, Ren Chenchun
Department of Clinical Laboratory, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, 300100, People's Republic of China.
Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
Adv Biol (Weinh). 2024 Feb;8(2):e2300451. doi: 10.1002/adbi.202300451. Epub 2023 Nov 27.
Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease with a certain degree of chronic inflammation and abnormal ovarian angiogenesis in reproductive women. Mesenchymal stem cells (MSCs) have potent immunomodulatory properties to regulate ovarian function, while thrombospondin 1 (TSP1) improves the abnormal formation of ovarian vessels. The present study investigated the efficacy of the combined use of adipose-derived mesenchymal stem cells (ADSCs) and TSP1 in PCOS mice. The PCOS model is established using dehydroepiandrosterone (DHEA) by subcutaneous injection. Ovarian apoptosis is assessed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Real-time quantitative PCR (RT-PCR) and western blotting are used to detect the expression of inflammatory factors and the levels of angiogenesis-related factors in ovarian tissues. Inflammatory cells count and ovarian angiogenesis are evaluated by immunofluorescence staining. This research shows that TSP1 and ADSCs treatment can significantly reduce the inflammatory state of PCOS mice, relieve the degree of ovarian cell apoptosis, optimize the ovarian histological manifestations, and restore the levels of related hormones. The proportion of CD31-positive cells in PCOS mice returned to near-normal levels. The synergistic use of ADSCs and TSP1 therapy can exert a more impressive effect by inhibiting the ovarian inflammatory response and regulating the balance of angiogenesis than the single application in PCOS mice.
多囊卵巢综合征(PCOS)是一种常见的妇科内分泌疾病,在育龄女性中存在一定程度的慢性炎症和卵巢血管生成异常。间充质干细胞(MSCs)具有强大的免疫调节特性以调节卵巢功能,而血小板反应蛋白1(TSP1)可改善卵巢血管的异常形成。本研究调查了脂肪来源的间充质干细胞(ADSCs)与TSP1联合使用对PCOS小鼠的疗效。通过皮下注射脱氢表雄酮(DHEA)建立PCOS模型。使用末端脱氧核苷酸转移酶dUTP缺口末端标记法(TUNEL)评估卵巢细胞凋亡。采用实时定量PCR(RT-PCR)和蛋白质印迹法检测卵巢组织中炎症因子的表达及血管生成相关因子的水平。通过免疫荧光染色评估炎症细胞计数和卵巢血管生成。本研究表明,TSP1和ADSCs治疗可显著降低PCOS小鼠的炎症状态,减轻卵巢细胞凋亡程度,优化卵巢组织学表现,并恢复相关激素水平。PCOS小鼠中CD31阳性细胞的比例恢复到接近正常水平。在PCOS小鼠中,ADSCs与TSP1联合治疗通过抑制卵巢炎症反应和调节血管生成平衡,比单一应用能发挥更显著的效果。