背景:多囊卵巢综合征(PCOS)是一种广泛存在于女性中的内分泌疾病,以卵巢囊肿等症状为特征,荷尔蒙失衡,和代谢问题。这项研究评估了骨髓间充质干细胞来源的外泌体(BMSC-Exo)在小鼠模型中治疗PCOS症状的治疗潜力。
方法:从NMRI小鼠中分离BMSC-Exo,用透射电子显微镜(TEM)和纳米粒子跟踪分析(NTA)表征,并给予脱氢表雄酮(DHEA)诱导的PCOS小鼠模型。在三组小鼠中评估BMSC-Exo的功效:对照组,PCOS组,和PCOS组静脉注射BMSC-Exo治疗。通过苏木精和伊红(H&E)染色检查卵巢组织的形态学变化,使用TUNEL测定法测定细胞凋亡,通过免疫荧光染色分析CD31表达以评估血管生成活性。
结果:通过TEM和NTA证实了BMSCs-Exo的存在,揭示其独特的杯形形态和30至150纳米的尺寸范围。H&E染色显示BMSCs-Exo治疗可改善PCOS模型的卵巢形态,增加黄体和振兴颗粒细胞层,提示PCOS诱导的损伤逆转。TUNEL分析显示BMSCs-Exo治疗可显著降低PCOS影响的卵巢细胞的凋亡,达到与对照组相当的水平。强调其在减轻PCOS诱导的细胞凋亡中的作用。CD31的免疫荧光表明BMSCs-Exo治疗使PCOS模型中的内皮标志物表达和血管生成活性正常化,提示其在调节PCOS血管不规则方面的有效性。总的来说,这些发现证明了BMSCs-Exo在解决卵巢功能障碍方面的治疗潜力,细胞凋亡,和与PCOS相关的异常血管生成。
结论:该研究证实了BMSC-Exo在减轻PCOS对卵巢组织的有害影响中的作用,与促进卵泡发育和减少细胞应激有关。BMSC-Exo对CD31的调节进一步强调了它们在使PCOS诱导的血管异常正常化中的潜力。这些发现推动了临床研究的需要,以探索BMSC-Exo作为PCOS管理的有希望的治疗途径。
BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a widespread endocrine disorder among women, characterized by symptoms like ovarian cysts, hormonal imbalance, and metabolic issues. This research evaluates the therapeutic potential of Bone Marrow Mesenchymal Stem Cell-derived exosomes (BMSC-Exo) in treating PCOS symptoms within a mouse model.
METHODS: BMSC-Exo were isolated from NMRI mice, characterized using Transmission Electron Microscopy (TEM) and Nanoparticle Tracking Analysis (NTA), and administered to a PCOS mouse model induced by dehydroepiandrosterone (DHEA). The efficacy of BMSC-Exo was assessed in three groups of mice: a control group, a PCOS group, and a PCOS group treated with intravenous BMSC-Exo. Morphological changes in ovarian tissue were examined by Hematoxylin and Eosin (H&E) staining, apoptosis was determined using the TUNEL assay, and CD31 expression was analyzed through immunofluorescent staining to assess angiogenic activity.
RESULTS: The existence of BMSCs-Exo was confirmed via TEM and NTA, revealing their distinct cup-shaped morphology and a size range of 30 to 150 nanometers. H&E staining revealed that BMSCs-Exo treatment improved ovarian morphology in PCOS models, increasing corpora lutea and revitalizing granulosa cell layers, suggesting a reversal of PCOS-induced damage. TUNEL assays showed that BMSCs-Exo treatment significantly reduced apoptosis in PCOS-affected ovarian cells to levels comparable with the control group, highlighting its role in mitigating PCOS-induced cellular apoptosis. Immunofluorescence for CD31 indicated that BMSCs-Exo treatment normalized endothelial marker expression and angiogenic activity in PCOS models, suggesting its effectiveness in modulating the vascular irregularities of PCOS. Collectively, these findings demonstrate the therapeutic potential of BMSCs-Exo in addressing ovarian dysfunction, cellular apoptosis, and aberrant angiogenesis associated with PCOS.
CONCLUSIONS: The study substantiates the role of BMSC-Exo in mitigating the deleterious effects of PCOS on ovarian tissue, with implications for enhanced follicular development and reduced cellular stress. The modulation of CD31 by BMSC-Exo further highlights their potential in normalizing PCOS-induced vascular anomalies. These findings propel the need for clinical investigations to explore BMSC-Exo as a promising therapeutic avenue for PCOS management.