Efficacy of umbilical cord mesenchymal stem cells transplantation in the treatment of premature ovarian failure: a meta-analysis of animal studies_Chinese Journal of Evidence-Based Medicine

Authors：

LI Ping ¹ ,  GUO Guangling ² , DONG Sirui ² , ZHAO Shuying ² , ZHANG Chao ³

1. Postgraduate Training Base, the Taihe Hospital of Hubei University of Medicine, Shiyan 442000, P. R. China;
2. Department of Women's Health Science Center, the Taihe Hospital of Hubei University of Medicine, Shiyan 442000, P. R. China;
3. Department of Evidence-Based Medicine Center, the Taihe Hospital of Hubei University of Medicine, Shiyan 442000, P. R. China;

Corresponding author：

GUO Guangling, Email: guoguangling@126.com

Keywords：

Umbilical cord mesenchymal stem cell; Premature ovarian failure; Animal experiment; Ovarian transplantation; Caudal vein transplantation; Meta-analysis; Systematic review

DOI：

10.7507/1672-2531.202110138

Video：

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Objective To systematically review the efficacy of umbilical cord mesenchymal stem cells in the treatment of premature ovarian failure. Methods CNKI, WanFang Data, SinoMed, PubMed and EMbase databases were electronically searched to collect animal experiments of the efficacy of umbilical cord mesenchymal stem cells in the treatment of premature ovarian failure from inception to September 17^th, 2021. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; then, meta-analysis was performed by using RevMan 5.4.1 software. Results A total of 9 studies involving 302 mice were included. The results of meta-analysis showed that: umbilical cord mesenchymal stem cell transplantation could increase primal follicles (SMD=1.51, 95%CI 0.80 to 2.22, P<0.000 1), primary follicles (SMD=1.43, 95%CI 0.76 to 2.09, P<0.000 1), secondary follicles (SMD=1.39, 95%CI 0.78 to 2.01, P<0.000 01) and sinus follicles (SMD=1.15, 95%CI 0.49 to 1.82, P=0.000 7). It significantly increased the concentration of estradiol in rats with premature ovarian failure (SMD=2.38, 95%CI 1.75 to 3.01, P<0.000 01), and decreased serum follicle-stimulating hormone concentration (SMD=−1.98, 95%CI −2.80 to −1.17, P<0.000 01). Conclusion Current evidence shows that umbilical cord mesenchymal stem cell transplantation can repair ovarian tissue and improve ovarian endocrine function in mice. Due to limited quality and quantity of the included studies, more high-quality studies are needed to verify above conclusions.

Citation： LI Ping, GUO Guangling, DONG Sirui, ZHAO Shuying, ZHANG Chao. Efficacy of umbilical cord mesenchymal stem cells transplantation in the treatment of premature ovarian failure: a meta-analysis of animal studies. Chinese Journal of Evidence-Based Medicine, 2022, 22(9): 1041-1047. doi: 10.7507/1672-2531.202110138 Copy

1.	徐晖. 卵巢早衰的治疗现状及进展. 中国现代医生, 2015, 53(21): 157-160.
2.	陈子江, 田秦杰, 乔杰, 等. 早发性卵巢功能不全的临床诊疗中国专家共识. 中华妇产科杂志, 2017, 52(9): 577-581.
3.	Zaher W, Harkness L, Jafari A, et al. An update of human mesenchymal stem cell biology and their clinical uses. Arch Toxicol, 2014, 88(5): 1069-1082.
4.	Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep, 2015, 35(2): e00191.
5.	Gabr H, Rateb MA, El Sissy MH, et al. The effect of bone marrow-derived mesenchymal stem cells on chemotherapy induced ovarian failure in albino rats. Microsc Res Tech, 2016, 79(10): 938-947.
6.	Li H, Zhao W, Wang L, et al. Human placenta-derived mesenchymal stem cells inhibit apoptosis of granulosa cells induced by IRE1α pathway in autoimmune POF mice. Cell Biol Int, 2019, 43(8): 899-909.
7.	Lu X, Cui J, Cui L, et al. The effects of human umbilical cord-derived mesenchymal stem cell transplantation on endometrial receptivity are associated with Th1/Th2 balance change and uNK cell expression of uterine in autoimmune premature ovarian failure mice. Stem Cell Res Ther, 2019, 10(1): 214.
8.	Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284(5411): 143-147.
9.	陈匡阳, 马彬, 王亚楠, 等. SYRCLE动物实验偏倚风险评估工具简介. 中国循证医学杂志, 2014, 14(10): 1281-1285.
10.	文进, 李幼平. Meta分析中效应尺度指标的选择. 中国循证医学杂志, 2007, 7(8): 606-613.
11.	朱少芳. 人脐带间充质干细胞移植改善化疗损伤卵巢功能的实验研究. 广州: 南方医科大学, 2011.
12.	付霞霏, 何援利. 脐带间充质干细胞移植对免疫性卵巢早衰的影响. 广东医学, 2013, 34(23): 3535-3538.
13.	Song D, Zhong Y, Qian C, et al. Human umbilical cord mesenchymal stem cells therapy in cyclophosphamide-induced premature ovarian failure rat model. Biomed Res Int, 2016, 2016: 2517514.
14.	钟韵. 人脐带血间充质干细胞治疗不同化疗药物致小鼠卵巢早衰的研究. 南京: 南京医科大学, 2017.
15.	Zheng Q, Fu X, Jiang J, et al. Umbilical cord mesenchymal stem cell transplantation prevents chemotherapy-induced ovarian failure via the NGF/TrkA pathway in rats. Biomed Res Int, 2019, 2019: 6539294.
16.	谭丽, 毛熙光, 钟影, 等. 人脐带间充质干细胞移植修复大鼠的卵巢早衰. 中国比较医学杂志, 2019, 29(10): 85-91.
17.	Shen J, Cao D, Sun JL. Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure. World J Stem Cells, 2020, 12(4): 277-287.
18.	Wang Z, Wei Q, Wang H, et al. Mesenchymal stem cell therapy using human umbilical cord in a rat model of autoimmune-induced premature ovarian failure. Stem Cells Int, 2020, 2020: 3249495.
19.	Zhang X, Zhang L, Li Y, et al. Human umbilical cord mesenchymal stem cells (hUCMSCs) promotes the recovery of ovarian function in a rat model of premature ovarian failure (POF). Gynecol Endocrinol, 2021, 37(4): 353-357.
20.	刘慧萍, 曾柳庭, 张国民, 等. 颗粒细胞与卵母细胞自噬对卵泡发育和闭锁的调控. 中华生殖与避孕杂志, 2017, 37(1): 67-74.
21.	张巧利. 甾体激素预处理在辅助生殖技术中的应用. 中华生殖与避孕杂志, 2018, 38(5): 427-431.
22.	郗红燕, 张杨, 赵小萱, 等. 卵巢早衰病理机制最新研究进展. 辽宁中医药大学学报, 2019, 21(12): 103-106.
23.	佟超. 线粒体异常与卵巢早衰. 山东大学学报(医学版), 2018, 56(4): 23-27.
24.	Meirelles Lda S, Fontes AM, Covas DT, et al. Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev, 2009, 20(5-6): 419-427.
25.	贺卫卫, 谢琪璇, 秦俊文, 等. 骨髓间充质干细胞对损伤卵巢的修复作用. 暨南大学学报(自然科学与医学版), 2010, 31(2): 120-124.
26.	李威娜, 谢琪璇, 秦俊文, 等. 骨髓间充质干细胞对免疫损伤卵巢的修复作用. 南方医科大学学报, 2011, 31(5): 825-829.
27.	Yin N, Wu C, Qiu J, et al. Protective properties of heme oxygenase-1 expressed in umbilical cord mesenchymal stem cells help restore the ovarian function of premature ovarian failure mice through activating the JNK/Bcl-2 signal pathway-regulated autophagy and upregulating the circulating of CD8⁺CD28^- T cells. Stem Cell Res Ther, 2020, 11(1): 49.
28.	Liu T, Huang Y, Zhang J, et al. Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model. Stem Cells Dev, 2014, 23(13): 1548-1557.
29.	李仲康. 间充质干细胞治疗卵巢早衰的最新进展及机制. 中国组织工程研究, 2022, 26(1): 145-152.

1. 徐晖. 卵巢早衰的治疗现状及进展. 中国现代医生, 2015, 53(21): 157-160.
2. 陈子江, 田秦杰, 乔杰, 等. 早发性卵巢功能不全的临床诊疗中国专家共识. 中华妇产科杂志, 2017, 52(9): 577-581.
3. Zaher W, Harkness L, Jafari A, et al. An update of human mesenchymal stem cell biology and their clinical uses. Arch Toxicol, 2014, 88(5): 1069-1082.
4. Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep, 2015, 35(2): e00191.
5. Gabr H, Rateb MA, El Sissy MH, et al. The effect of bone marrow-derived mesenchymal stem cells on chemotherapy induced ovarian failure in albino rats. Microsc Res Tech, 2016, 79(10): 938-947.
6. Li H, Zhao W, Wang L, et al. Human placenta-derived mesenchymal stem cells inhibit apoptosis of granulosa cells induced by IRE1α pathway in autoimmune POF mice. Cell Biol Int, 2019, 43(8): 899-909.
7. Lu X, Cui J, Cui L, et al. The effects of human umbilical cord-derived mesenchymal stem cell transplantation on endometrial receptivity are associated with Th1/Th2 balance change and uNK cell expression of uterine in autoimmune premature ovarian failure mice. Stem Cell Res Ther, 2019, 10(1): 214.
8. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284(5411): 143-147.
9. 陈匡阳, 马彬, 王亚楠, 等. SYRCLE动物实验偏倚风险评估工具简介. 中国循证医学杂志, 2014, 14(10): 1281-1285.
10. 文进, 李幼平. Meta分析中效应尺度指标的选择. 中国循证医学杂志, 2007, 7(8): 606-613.
11. 朱少芳. 人脐带间充质干细胞移植改善化疗损伤卵巢功能的实验研究. 广州: 南方医科大学, 2011.
12. 付霞霏, 何援利. 脐带间充质干细胞移植对免疫性卵巢早衰的影响. 广东医学, 2013, 34(23): 3535-3538.
13. Song D, Zhong Y, Qian C, et al. Human umbilical cord mesenchymal stem cells therapy in cyclophosphamide-induced premature ovarian failure rat model. Biomed Res Int, 2016, 2016: 2517514.
14. 钟韵. 人脐带血间充质干细胞治疗不同化疗药物致小鼠卵巢早衰的研究. 南京: 南京医科大学, 2017.
15. Zheng Q, Fu X, Jiang J, et al. Umbilical cord mesenchymal stem cell transplantation prevents chemotherapy-induced ovarian failure via the NGF/TrkA pathway in rats. Biomed Res Int, 2019, 2019: 6539294.
16. 谭丽, 毛熙光, 钟影, 等. 人脐带间充质干细胞移植修复大鼠的卵巢早衰. 中国比较医学杂志, 2019, 29(10): 85-91.
17. Shen J, Cao D, Sun JL. Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure. World J Stem Cells, 2020, 12(4): 277-287.
18. Wang Z, Wei Q, Wang H, et al. Mesenchymal stem cell therapy using human umbilical cord in a rat model of autoimmune-induced premature ovarian failure. Stem Cells Int, 2020, 2020: 3249495.
19. Zhang X, Zhang L, Li Y, et al. Human umbilical cord mesenchymal stem cells (hUCMSCs) promotes the recovery of ovarian function in a rat model of premature ovarian failure (POF). Gynecol Endocrinol, 2021, 37(4): 353-357.
20. 刘慧萍, 曾柳庭, 张国民, 等. 颗粒细胞与卵母细胞自噬对卵泡发育和闭锁的调控. 中华生殖与避孕杂志, 2017, 37(1): 67-74.
21. 张巧利. 甾体激素预处理在辅助生殖技术中的应用. 中华生殖与避孕杂志, 2018, 38(5): 427-431.
22. 郗红燕, 张杨, 赵小萱, 等. 卵巢早衰病理机制最新研究进展. 辽宁中医药大学学报, 2019, 21(12): 103-106.
23. 佟超. 线粒体异常与卵巢早衰. 山东大学学报(医学版), 2018, 56(4): 23-27.
24. Meirelles Lda S, Fontes AM, Covas DT, et al. Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev, 2009, 20(5-6): 419-427.
25. 贺卫卫, 谢琪璇, 秦俊文, 等. 骨髓间充质干细胞对损伤卵巢的修复作用. 暨南大学学报(自然科学与医学版), 2010, 31(2): 120-124.
26. 李威娜, 谢琪璇, 秦俊文, 等. 骨髓间充质干细胞对免疫损伤卵巢的修复作用. 南方医科大学学报, 2011, 31(5): 825-829.
27. Yin N, Wu C, Qiu J, et al. Protective properties of heme oxygenase-1 expressed in umbilical cord mesenchymal stem cells help restore the ovarian function of premature ovarian failure mice through activating the JNK/Bcl-2 signal pathway-regulated autophagy and upregulating the circulating of CD8⁺CD28^- T cells. Stem Cell Res Ther, 2020, 11(1): 49.
28. Liu T, Huang Y, Zhang J, et al. Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model. Stem Cells Dev, 2014, 23(13): 1548-1557.
29. 李仲康. 间充质干细胞治疗卵巢早衰的最新进展及机制. 中国组织工程研究, 2022, 26(1): 145-152.

Chinese Journal of Evidence-Based Medicine

Efficacy of umbilical cord mesenchymal stem cells transplantation in the treatment of premature ovarian failure: a meta-analysis of animal studies

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