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.	徐暉. 卵巢早衰的治療現狀及進展. 中國現代醫生, 2015, 53(21): 157-160.
2.	陳子江, 田秦杰, 喬杰, 等. 早發性卵巢功能不全的臨床診療中國專家共識. 中華婦產科雜志, 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.	陳匡陽, 馬彬, 王亞楠, 等. SYRCLE動物實驗偏倚風險評估工具簡介. 中國循證醫學雜志, 2014, 14(10): 1281-1285.
10.	文進, 李幼平. Meta分析中效應尺度指標的選擇. 中國循證醫學雜志, 2007, 7(8): 606-613.
11.	朱少芳. 人臍帶間充質干細胞移植改善化療損傷卵巢功能的實驗研究. 廣州: 南方醫科大學, 2011.
12.	付霞霏, 何援利. 臍帶間充質干細胞移植對免疫性卵巢早衰的影響. 廣東醫學, 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.	鐘韻. 人臍帶血間充質干細胞治療不同化療藥物致小鼠卵巢早衰的研究. 南京: 南京醫科大學, 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.	譚麗, 毛熙光, 鐘影, 等. 人臍帶間充質干細胞移植修復大鼠的卵巢早衰. 中國比較醫學雜志, 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.	劉慧萍, 曾柳庭, 張國民, 等. 顆粒細胞與卵母細胞自噬對卵泡發育和閉鎖的調控. 中華生殖與避孕雜志, 2017, 37(1): 67-74.
21.	張巧利. 甾體激素預處理在輔助生殖技術中的應用. 中華生殖與避孕雜志, 2018, 38(5): 427-431.
22.	郗紅燕, 張楊, 趙小萱, 等. 卵巢早衰病理機制最新研究進展. 遼寧中醫藥大學學報, 2019, 21(12): 103-106.
23.	佟超. 線粒體異常與卵巢早衰. 山東大學學報(醫學版), 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.	賀衛衛, 謝琪璇, 秦俊文, 等. 骨髓間充質干細胞對損傷卵巢的修復作用. 暨南大學學報(自然科學與醫學版), 2010, 31(2): 120-124.
26.	李威娜, 謝琪璇, 秦俊文, 等. 骨髓間充質干細胞對免疫損傷卵巢的修復作用. 南方醫科大學學報, 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. 間充質干細胞治療卵巢早衰的最新進展及機制. 中國組織工程研究, 2022, 26(1): 145-152.

1. 徐暉. 卵巢早衰的治療現狀及進展. 中國現代醫生, 2015, 53(21): 157-160.
2. 陳子江, 田秦杰, 喬杰, 等. 早發性卵巢功能不全的臨床診療中國專家共識. 中華婦產科雜志, 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. 陳匡陽, 馬彬, 王亞楠, 等. SYRCLE動物實驗偏倚風險評估工具簡介. 中國循證醫學雜志, 2014, 14(10): 1281-1285.
10. 文進, 李幼平. Meta分析中效應尺度指標的選擇. 中國循證醫學雜志, 2007, 7(8): 606-613.
11. 朱少芳. 人臍帶間充質干細胞移植改善化療損傷卵巢功能的實驗研究. 廣州: 南方醫科大學, 2011.
12. 付霞霏, 何援利. 臍帶間充質干細胞移植對免疫性卵巢早衰的影響. 廣東醫學, 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. 鐘韻. 人臍帶血間充質干細胞治療不同化療藥物致小鼠卵巢早衰的研究. 南京: 南京醫科大學, 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. 譚麗, 毛熙光, 鐘影, 等. 人臍帶間充質干細胞移植修復大鼠的卵巢早衰. 中國比較醫學雜志, 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. 劉慧萍, 曾柳庭, 張國民, 等. 顆粒細胞與卵母細胞自噬對卵泡發育和閉鎖的調控. 中華生殖與避孕雜志, 2017, 37(1): 67-74.
21. 張巧利. 甾體激素預處理在輔助生殖技術中的應用. 中華生殖與避孕雜志, 2018, 38(5): 427-431.
22. 郗紅燕, 張楊, 趙小萱, 等. 卵巢早衰病理機制最新研究進展. 遼寧中醫藥大學學報, 2019, 21(12): 103-106.
23. 佟超. 線粒體異常與卵巢早衰. 山東大學學報(醫學版), 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. 賀衛衛, 謝琪璇, 秦俊文, 等. 骨髓間充質干細胞對損傷卵巢的修復作用. 暨南大學學報(自然科學與醫學版), 2010, 31(2): 120-124.
26. 李威娜, 謝琪璇, 秦俊文, 等. 骨髓間充質干細胞對免疫損傷卵巢的修復作用. 南方醫科大學學報, 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. 間充質干細胞治療卵巢早衰的最新進展及機制. 中國組織工程研究, 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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