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人脐带间充质干细胞通过旁分泌机制改善围绝经期卵巢储备功能。

Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism.

作者信息

Li Jia, Mao QiuXian, He JingJun, She HaoQing, Zhang Zhi, Yin ChunYan

机构信息

Department of Obstetrics and Gynecology, Graduate College, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.

Department of Obstetrics and Gynecology, Guangdong No.2 Provincial People's Hospital, NO.466 Xingangdong Road, Guangzhou, 510317, China.

出版信息

Stem Cell Res Ther. 2017 Mar 9;8(1):55. doi: 10.1186/s13287-017-0514-5.

Abstract

BACKGROUND

Human umbilical cord mesenchymal stem cells (hUCMSCs) are a type of pluripotent stem cell which are isolated from the umbilical cord of newborns. hUCMSCs have great therapeutic potential. We designed this experimental study in order to investigate whether the transplantation of hUCMSCs can improve the ovarian reserve function of perimenopausal rats and delay ovarian senescence.

METHOD

We selected naturally aging rats confirmed by vaginal smears as models of perimenopausal rats, divided into the control group and the treatment group, and selected young fertile female rats as normal controls. hUCMSCs were transplanted into rats of the treatment group through tail veins. Enzyme-linked immunosorbent assay (ELISA) detected serum levels of sex hormones, H&E staining showed ovarian tissue structure and allowed follicle counting, immunohistochemistry and western blot analysis revealed ovarian expression of hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF), and insulin-like growth factor-1 (IGF-1), polymerase chain reaction (PCR) and western blot analysis revealed hUCMSCs expression of HGF, VEGF, and IGF-1.

RESULTS

At time points of 14, 21, and 28 days after hUCMSCs transplantation, estradiol (E) and anti-Müllerian hormone (AMH) increased while follicle-stimulating hormone (FSH) decreased; ovarian structure improved and follicle number increased; ovarian expression of HGF, VEGF, and IGF-1 protein elevated significantly. Meanwhile, PCR and western blot analysis indicated hUCMSCs have the capacity of secreting HGF, VEGF, and IGF-1 cytokines.

CONCLUSIONS

Our results suggest that hUCMSCs can promote ovarian expression of HGF, VEGF, and IGF-1 through secreting those cytokines, resulting in improving ovarian reserve function and withstanding ovarian senescence.

摘要

背景

人脐带间充质干细胞(hUCMSCs)是一种从新生儿脐带中分离出来的多能干细胞。hUCMSCs具有巨大的治疗潜力。我们设计了这项实验研究,以探讨hUCMSCs移植是否能改善围绝经期大鼠的卵巢储备功能并延缓卵巢衰老。

方法

我们选择经阴道涂片确认的自然衰老大鼠作为围绝经期大鼠模型,分为对照组和治疗组,并选择年轻的育龄雌性大鼠作为正常对照。通过尾静脉将hUCMSCs移植到治疗组大鼠体内。酶联免疫吸附测定(ELISA)检测血清性激素水平,苏木精-伊红(H&E)染色显示卵巢组织结构并进行卵泡计数,免疫组织化学和蛋白质印迹分析揭示卵巢中肝细胞生长因子(HGF)、血管内皮细胞生长因子(VEGF)和胰岛素样生长因子-1(IGF-1)的表达,聚合酶链反应(PCR)和蛋白质印迹分析揭示hUCMSCs中HGF、VEGF和IGF-1的表达。

结果

在hUCMSCs移植后14、21和28天的时间点,雌二醇(E)和抗苗勒管激素(AMH)升高而促卵泡生成素(FSH)降低;卵巢结构改善且卵泡数量增加;卵巢中HGF、VEGF和IGF-1蛋白的表达显著升高。同时,PCR和蛋白质印迹分析表明hUCMSCs具有分泌HGF、VEGF和IGF-1细胞因子的能力。

结论

我们的结果表明,hUCMSCs可通过分泌这些细胞因子促进卵巢中HGF、VEGF和IGF-1的表达,从而改善卵巢储备功能并抵抗卵巢衰老。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/239e/5345137/fba66d69838d/13287_2017_514_Fig1_HTML.jpg

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