Department of Obstetrics and Gynecology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Stem Cell Rev Rep. 2024 Feb;20(2):538-553. doi: 10.1007/s12015-023-10629-8. Epub 2023 Dec 4.
Premature ovarian insufficiency (POI) is a relatively common gynecologic endocrine disorder, which is hypogonadism associated with amenorrhea, increased levels of gonadotropins, and hypoestrogenism. POI resulting from ovarian autoimmunity is a poorly understood clinical condition lacking effective treatments. This study is aimed to investigate the therapeutic effect of mesenchymal stem cells (MSCs) on autoimmune premature ovarian insufficiency.
In this study, in vivo and in vitro experiments were conducted to clarify the therapeutic effects and possible mechanisms of human bone marrow-derived MSCs (hBMSCs) on autoimmune POI, and to provide an experimental evidence for the treatment of autoimmune POI by hBMSCs. Noteworthy, in this study, we used interferon-gamma (IFN-γ) to induce autoimmune inflammation in human granulosa cell line KGN, simulating the pathophysiological changes of granulosa cells in autoimmune POI, and therefore sought to establish an in vitro cell model of autoimmune POI, which is still lacking in experimental methodology.
And we found that, in vitro, co-culture of hBMSCs could promote granulosa cell proliferation, inhibit apoptosis, improve hormone synthesis capacity, and reduce the occurrence of pyroptosis; and in vivo, hBMSCs resulted in improved estrous cycle disorders in autoimmune POI mice, increased serum estradiol, decreased follicle-stimulating hormone, improved ovarian morphology, increased number of primordial and primary follicles, decreased number of atretic follicles, and decreased ovarian granulosa cell apoptosis.
hBMSCs have therapeutic effects on autoimmune POI both in vitro and in vivo.
卵巢早衰(POI)是一种较为常见的妇科内分泌疾病,是一种与闭经、促性腺激素水平升高和雌激素水平降低相关的性腺功能减退症。由卵巢自身免疫引起的 POI 是一种临床情况尚不清楚且缺乏有效治疗方法的疾病。本研究旨在探讨间充质干细胞(MSCs)对自身免疫性卵巢早衰的治疗作用。
本研究通过体内和体外实验,阐明了人骨髓来源的间充质干细胞(hBMSCs)对自身免疫性 POI 的治疗作用及其可能的机制,为 hBMSCs 治疗自身免疫性 POI 提供了实验依据。值得注意的是,在本研究中,我们使用干扰素-γ(IFN-γ)诱导人颗粒细胞系 KGN 发生自身免疫性炎症,模拟自身免疫性 POI 中颗粒细胞的病理生理变化,因此试图建立自身免疫性 POI 的体外细胞模型,这在实验方法学上仍然缺乏。
我们发现,体外共培养 hBMSCs 可促进颗粒细胞增殖、抑制凋亡、提高激素合成能力、减少细胞焦亡的发生;体内 hBMSCs 可改善自身免疫性 POI 小鼠的动情周期紊乱,增加血清雌二醇,降低卵泡刺激素,改善卵巢形态,增加原始卵泡和初级卵泡数量,减少闭锁卵泡数量,减少卵巢颗粒细胞凋亡。
hBMSCs 对自身免疫性 POI 具有体内外的治疗作用。