低氧预处理人脐带间充质干细胞治疗早发性卵巢功能不全小鼠的效果研究

doi:10.3969/j.issn.1006-7795.2019.04.014

首都医科大学学报 ›› 2019, Vol. 40 ›› Issue (4): 566-571.doi: 10.3969/j.issn.1006-7795.2019.04.014

低氧预处理人脐带间充质干细胞治疗早发性卵巢功能不全小鼠的效果研究

赵越¹, 阮祥燕^1,2, 王凤春³, 李扬璐¹, 程姣姣¹, Alfred O. Mueck^1,2

1. 首都医科大学附属北京妇产医院内分泌科, 北京 100026;
2. 德国图宾根大学妇产医院妇女健康部与妇女健康研究中心, 图宾根 D-72076, 德国;
3. 首都医科大学附属北京妇产医院产房, 北京 100026

收稿日期:2019-05-20 出版日期:2019-07-21 发布日期:2019-07-19
通讯作者: 阮祥燕 E-mail:ruanxiangyan@163.com
基金资助:
北京市医院管理局"青苗"计划专项经费资助（QML20181401），首都医科大学科研培育基金（PYZ2018161），首都医科大学附属北京妇产医院中青年学科骨干培养专项（FCYY201811），北京市医院管理局临床技术创新项目（XMLX201710），首都临床特色应用研究与推广项目（Z161100000516143）。

Therapeutic effect of hypoxia-preconditioned human umbilical cord mesenchymal stem cell on premature ovarian insufficiency mouse model

Zhao Yue¹, Ruan Xiangyan^1,2, Wang Fengchun³, Li Yanglu¹, Cheng Jiaojiao¹, Alfred O. Mueck^1,2

1. Department of Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China;
2. Department for Women's Health, University Women's Hospital and Research Center for Women's Health, University of Tuebingen, Tuebingen D-72076, Germany;
3. Department of Delivery, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China

Received:2019-05-20 Online:2019-07-21 Published:2019-07-19
Supported by:
This study was supported by Beijing Municipal Administration of Hospital' Youth Programme (QML20181401), Capital Medical University Research and Development Fund (PYZ2018161),Beijing Obstetrics and Gynecology Hospital, Capital Medical University (FCYY201811),Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(XMLX201710), Beijing Municipal Science and Technology Commission (Z161100000516143).

摘要/Abstract

摘要： 目的探索人脐带间充质干细胞（human umbilical cord mesenchymal stem cells，hUCMSCs）及其经低氧预处理后对早发性卵巢功能不全（premature ovarian insufficiency，POI）小鼠的治疗作用。方法从脐带中分离、培养出hUCMSCs，利用白消安和环磷酰胺诱导形成小鼠POI模型，分别使用正常hUCMSCs和经低氧预处理的hUCMSCs对POI小鼠进行治疗。实验结束时，测量各组（n=15）小鼠血浆中雌二醇（estradiol，E2）、卵泡刺激素（follicle stimulating hormone，FSH）及抗苗勒管激素（anti Mullerian hormone，AMH）浓度，对卵巢进行组织病理学检查，计数卵泡数量。结果经过hUCMSCs和低氧预处理hUCMSCs治疗的小鼠血浆E2及AMH浓度，与模型对照组比较，呈升高趋势；且AMH浓度差异有统计学意义（P<0.05）；与模型对照组比较，hUCMSCs和低氧预处理hUCMSCs治疗组小鼠卵巢组织中生长卵泡明显增多、闭锁卵泡明显减少（P<0.05）；卵巢颜色红润，尺寸增大，几乎没有坏死点，卵泡大、透明度好，整体来看与正常对照组卵巢状态相似；且经低氧预处理hUCMSCs治疗的小鼠，其生长卵泡和闭锁卵泡数量更趋于正常。结论 hUCMSCs移植及hUCMSCs低氧预处理后移植治疗均能够有效恢复POI小鼠的激素浓度，促进卵巢功能的恢复。

关键词: 人脐带间充质干细胞, 早发性卵巢功能不全, 卵巢早衰, 动物实验

Abstract: Objective To investigate the therapeutic effect of hypoxia-preconditioned human umbilical cord mesenchymal stem cells (hUCMSCs) on premature ovarian insufficiency (POI) mice model. Methods hUCMSCs were isolated and cultured from umbilical cord, and POI mice model were induced by busulfan and cyclophosphamide. POI mice were treated with normal hUCMSCs and hypoxic pretreated hUCMSCs. At the end of the experiment, the levels of estradiol (E2), follicle stimulating hormone (FSH) and anti Mullerian hormone (AMH) in the plasma were measured, histopathological examination was performed on ovaries, and the number of follicles was counted. Results Plasma E2 and AMH levels in mice treated with hUCMSCs and hypoxic preconditioned hUCMSCs showed an increasing trend, with a significantly different in AMH levels (P<0.05) compared with the control group. The growth of follicles in the ovarian tissue of the hUCMSCs and hypoxic preconditioned hUCMSCs groups was significantly increased, and the atresia follicles were significantly decreased (P<0.05). The color of the ovary was ruddy, and the size was increased, with almost no necrosis. The follicles were large, with good transparency. The ovarian status of the normal control group was similar, and the number of growing follicles and atresia follicles in the treated groups became more normal. Conclusion hUCMSCs transplantation significantly improved the serum levels of high gonadotropin and low estrogen of POI mice, and promote follicular development.

Key words: human umbilical cord mesenchymal stem cells, premature ovarian insufficiency, premature ovarian failure, animal experiment

中图分类号:

R711

赵越, 阮祥燕, 王凤春, 李扬璐, 程姣姣, Alfred O. Mueck. 低氧预处理人脐带间充质干细胞治疗早发性卵巢功能不全小鼠的效果研究[J]. 首都医科大学学报, 2019, 40(4): 566-571.

Zhao Yue, Ruan Xiangyan, Wang Fengchun, Li Yanglu, Cheng Jiaojiao, Alfred O. Mueck. Therapeutic effect of hypoxia-preconditioned human umbilical cord mesenchymal stem cell on premature ovarian insufficiency mouse model[J]. Journal of Capital Medical University, 2019, 40(4): 566-571.

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低氧预处理人脐带间充质干细胞治疗早发性卵巢功能不全小鼠的效果研究

Therapeutic effect of hypoxia-preconditioned human umbilical cord mesenchymal stem cell on premature ovarian insufficiency mouse model

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