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中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2024, Vol. 14 ›› Issue (04) : 239 -248. doi: 10.3877/cma.j.issn.2095-1221.2024.04.007

综述

干细胞治疗早发性卵巢功能不全的现状及未来展望
陈丽璇1, 窦培宁2, 肖扬1,†()   
  1. 1. 518067，深圳市前海蛇口自贸区医院血液科
    2. 510515　广州，南方医科大学第一临床医学院
  • 收稿日期:2024-04-17 出版日期:2024-08-01
  • 通信作者: 肖扬
  • 基金资助:
    吴阶平医学基金会临床科研专项(320.6750.2021-04-43); 2022年深圳市南山区卫生局卫生科技项目(NS2022004); 深圳市科技计划项目(JCYJ20220530151613030)

Progress and future prospects of stem cell therapy for premature ovarian insufficiency

Lixuan Chen1, Peining Dou2, Yang Xiao1,†()   

  1. 1. Department of Hematology, Shenzhen Qianhai Shekou Pilot Free Trade Zone Hospital, Shenzhen 518067, China
    2. The First Clinical Medical College, Southern Medical University, Guang zhou 510515, China
  • Received:2024-04-17 Published:2024-08-01
  • Corresponding author: Yang Xiao
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陈丽璇, 窦培宁, 肖扬. 干细胞治疗早发性卵巢功能不全的现状及未来展望[J]. 中华细胞与干细胞杂志(电子版), 2024, 14(04): 239-248.

Lixuan Chen, Peining Dou, Yang Xiao. Progress and future prospects of stem cell therapy for premature ovarian insufficiency[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(04): 239-248.

早发性卵巢功能不全（POI）是一种女性卵巢功能障碍的疾病，发病原因复杂，近年来发病率呈上升趋势。POI是导致女性不孕的主要因素之一，而目前激素替代治疗并不能有效恢复患者生殖能力。干细胞具有自我更新、损伤修复和多向分化等生物学功能，是治疗POI的新思路，然而目前其临床应用研究的结果却仍不理想。本文从干细胞治疗POI的细胞种类、作用机制、研究现状和未来潜力进行总结分析，并对影响干细胞治疗POI的疗效因素和提高其疗效的方法进行讨论分析，为更好地开展干细胞治疗POI的临床研究提供参考。

关键词: 干细胞, 早发性卵巢功能不全, 作用机制, 临床研究

Premature ovarian insufficiency (POI) is a disease of female ovarian dysfunction with complex etiology, and its incidence has shown an upward trend in recent years. POI is one of the main factors leading to female infertility, and current hormone replacement therapy cannot effectively restore the patient's reproductive ability. Stem cells have biological functions such as self-renewal, damage repair and multi-directional differentiation, which is a new approach to treating POI. However, the results of clinical application research are still unsatisfactory. This article discusses and analyzes the potential and mechanism of stem cells in the treatment of POI and its clinical research progress. It also summarizes the factors that affect the efficacy of stem cell therapy and the methods to improve its effectiveness, providing a reference for further research on stem cell therapy for POI.

Key words: Stem cell, Premature ovarian insufficiency, Mechanism, Clinical research
图1 干细胞治疗POI的作用机制注：VEGF为血管内皮生长因子；HGF为肝细胞再生因子；bFGF为碱性成纤维细胞生长因子；IL-6为白介素6；IL-10为白介素10；TNF-α为肿瘤坏死因子α；TGF-β为转化生长因子β
表1 我国干细胞治疗POI/POF临床研究备案项目
项目名称 机构名称 备案时间
POF合并不孕症患者hUC-MSCs移植干预的临床研究 南京大学医学院附属鼓楼医院 2017.03
hESCs来源间充质样细胞治疗POI的临床耐受性研究 郑州大学第一附属医院 2019.01
hUC-MSCs治疗POI的安全性和初步有效性研究 广州医科大学附属第三医院 2019.06
hUC-MSCs治疗POI的临床研究 南京大学医学院附属鼓楼医院 2019.09
人羊膜上皮干细胞移植治疗POF的临床研究 中国福利会国际和平妇幼保健院 2019.12
人羊膜来源MSCs改善卵巢功能减退女性生育结局的临床研究 江苏省人民医院 2020.11
hUC-MSCs卵巢原位注射治疗POI的安全性和有效性临床研究 浙江大学医学院邵逸夫医院 2021.11
表2 ClinicalTrials.gov注册的干细胞治疗POI/POF的项目
注册号 研究题目 开始时间/状态 国家
NCT02151890 卵巢早衰干细胞移植后的妊娠 2012.03 /完成 埃及
NCT02372474 卵巢早衰自体干细胞治疗的第一个婴儿 2012.03/完成 埃及
NCT02062931 自体间充质干细胞治疗治疗卵巢早衰 2012.03/未知 埃及
NCT01742533 干细胞联合激素替代治疗早发性卵巢早衰 2012.03/未知 中国
NCT01853501 ADSC治疗卵巢早衰患者的效果 2012.09/未知 中国
NCT02043743 自体干细胞移植治疗特发性和药物诱导性的卵巢早衰 2014.01/未知 埃及
NCT03069209 自体骨髓干细胞移植治疗卵巢早衰 2015.01/未知 约旦
NCT02603744 自体脂肪间充质干细胞治疗卵巢早衰 2015.06/未知 伊朗
NCT02644447 可注射胶原支架携载HUC-MSCs移植治疗卵巢早衰 2015.10/完成 中国
NCT02696889 自体干细胞治疗早发性卵巢功能不全和卵巢储备低下 2016.02/完成 美国
NCT03033277 人脐带间充质干细胞治疗早发性卵巢功能不全 2016.02/未知 中国
NCT02779374 自体骨髓移植治疗早发性卵巢功能不全 2016.07/终止 埃及
NCT03535480 自体骨髓干细胞卵巢移植恢复卵巢早衰患者的卵巢功能 2018.06/未知 西班牙
NCT03816852 间充质干细胞治疗早发性卵巢功能不全的安全性和有效性研究 2018.10/暂停 中国
NCT05138367 UCA-PSCs治疗卵巢早衰的效果 2018.12/完成 中国
NCT03877471 间充质干细胞样细胞移植治疗早发性卵巢功能不全 2019.04/未知 中国
NCT04009473 富血小板血浆用于卵巢体外活化和干细胞移植治疗 2019.06/未知 马尔他
NCT05308342 人脐带间充质干细胞治疗早发性卵巢功能不全的临床研究 2019.11/未知 中国
NCT04475744 4-step ASCOT技术治疗早发性卵巢功能不全 202.03/完成 西班牙
NCT06132542 自体脂肪间充质干细胞治疗早发性卵巢功能不全 2024.01/未招募 蒙古
NCT05494723 YB-1113治疗早发性卵巢功能不全的安全性和有效性研究 2024.01/未招募 美国
表3 干细胞治疗POI/POF临床试验的结果
登记号 研究类型 患者情况 细胞类型及剂量 给药途径
/ 非随机、开放性试验、单臂 10例卵巢早衰患者 自体BMSCs，10 mL 腹腔镜下卵巢注射
NCT02644447 单中心，随机对照 14例卵巢早衰患者，6例接受hUC-MSCs移植；8例接受hUC-MSCs联合胶原支架移植 hUC-MSCs，1×107cells（5×106/侧） 经阴道超声引导行卵巢注射
NCT02240342 非随机、开放性试验、单臂 17例卵巢储备功能低下及体外受精卵巢反应不良患者 自体骨髓干细胞（CD 133+细胞），5×107 经一侧动脉内导管输送至卵巢动脉
/ 病例报告 1例45岁围绝经期女性 自体BMSCs，1 ~ 2 mL 腹腔镜下卵巢注射
NCT03033277 非随机、单臂 141例早发性卵巢功能不全患者，分组接受不同频次的干细胞治疗 hUC-MSCs，1×107cells （5×106/侧） 经阴道超声引导行卵巢注射
NCT02696889 病例报告 1例卵巢早衰患者（停用口服避孕药后继发性闭经）；1例卵巢早衰患者（左侧卵巢囊肿切除术后继发性闭经） 自体BMSCs，4 mL （约5×108有核细胞，平均5 ~ 15×106 MSCs） 腹腔镜下卵巢注射
NCT02603744 非随机、I期、开放性试验 9例卵巢早衰患者，分组接受不同剂量的干细胞移植治疗 自体ADSCs；G1：5×106（n = 3）；G2：10×106（n = 3）；G3:15×106 （n = 3） 经阴道超声引导行卵巢注射
登记号 给药次数 随访 主要结果 参考文献
/ 单次 1年 2例在移植后3个月后恢复月经，出现局灶性分泌期子宫内膜和变形增生期子宫内膜；其中1例在11个月后妊娠并分娩。 [76]
NCT02644447 单次 1年 移植后3个月，两组性激素水平改善，但胶原/hUC-MSCs组FSH水平降低；两组各有1例在移植后1年内自然受孕。胶原蛋白携载组女性因为胎儿21三体综合征于孕24周引产。 [83]
NCT02240342 单次 5个月 81.3%患者的卵巢功能改善，治疗2周后窦卵泡数量增加；随访期间实现了5次妊娠（3次是自然受孕），共分娩3个健康婴儿。 [80]
/ 单次 > 1年 治疗后8周取卵，行冷冻胚胎移植，成功妊娠及分娩。 [81]
NCT03033277 单次（n = 61）；2次（n = 50）；3次（n = 30） 6个月 患者的卵巢功能（卵泡发育增加和卵子收集改善）；4例患者妊娠并分娩。 [79]
NCT02696889 单次   与对侧对照卵巢相比，治疗卵巢的体积增加了约50%，雌激素水平增加了约150%。移植后7个月，两例患者围绝经期症状改善，均有1次月经。 [77]
NCT02603744 单次 1年 1.在高剂量组2例患者在治疗后2个月恢复月经；低、中剂量组各有1例在治疗后1个月恢复月经。
2.有4例患者FSH水平低于25 IU/L；各组间比较差异无统计学意义。		 [78]
1
Rudnicka E, Kruszewska J, Klicka K, et al. Premature ovarian insufficiency-aetiopathology, epidemiology, and diagnostic evaluation[J]. Prz Menopauzalny, 2018, 17(3):105-108.
2
Webber L, Davies M, Anderson R, et al. European society for human reproduction and embryology (ESHRE) guideline group on POI. ESHRE guideline: management of women with premature ovarian insufficiency[J]. Hum Reprod, 2016, 31(5):926-937.
3
Coulam CB, Adamson SC, Annegers JF. Incidence of premaure ovarian failure[J]. Obstet Gynecol, 1986, 67(4):604-606.
4
Luborsky JL, Meyer P, Sowers MF, et al. Premature menopause in a multi-ethnic population study of the menopause transition[J]. Hum Reprod, 2003, 18(1):199-206.
5
Lagergeren K, Hammar M, Nedstrand E, et al. The prevalence of primary ovarian insufficiency in Sweden; a national register study[J]. BMC Womens Health, 2018, 18(1):175.doi: 10.1186/s12905-018-0665-2.
6
Golezar S, Ramezani TF, Khazaei S, et al. The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis[J]. Climacteric, 2019, 22(4):403-411.
7
Zhou Y, Zhou J, Xu X, et al. Matrigel/umbilical cord-derived mesenchymal stem cells promote granulosa cell proliferation and ovarian vascularization in a mouse model of premature ovarian failure[J]. Stem Cells Dev, 2021, 30(15):782-796.
8
Abd-Allah SH, Shalaby SM, Pasha HF, et al. Mechanistic action of mesenchymal stem cell injection in the treatment of chemically induced ovarian failure in rabbits[J]. Cytotherapy, 2013, 15(1):64-75.
9
Xia X, Yin T, Yan J, et al. Mesenchymal stem cells enhance angiogenesis and follicle survival in human cryopreserved ovarian cortex transplantation[J]. Cell Transplant, 2015, 24(10):1999-2010.
10
Wang Z, Wang Y, Yang T, et al. Study of the reparative effects of menstrual-derived stem cells on premature ovarian failure in mice[J]. Stem Cell Res Ther, 2017, 8(1):11-25.
11
Cui L, Bao H, Zhu W, et al. hUMSCs Transplantation regulates AMPK/NR4A1 signaling axis to inhibit ovarian fibrosis in POI rats[J]. Stem Cell Rev Rep, 2023, 19(5):1449-1465.
12
Zhao Y, Ma J, Yi P, et al. Human umbilical cord mesenchymal stem cells restore the ovarian metabolome and rescue premature ovarian insufficiency in mice[J]. Stem Cell Res Ther, 2020, 11(1):466. doi: 10.1186/s13287-020-01972-5.
13
Huang BX, Qian CF, Ding CY, et al. Fetal liver mesenchymal stem cells restore ovarian function in prematureovarian insufficiency by targeting MT1[J]. Stem Cell Res Ther, 2019, 10(1):362. doi: 10.1186/s13287-019-1490-8.
14
Yin N, Zhao W, Luo Q, et al. Restoring ovarian function with human placenta-derived mesenchymal stem cells in autoimmune-induced premature ovarian failure mice mediated by Treg cells and associated cytokines[J]. Reprod Sci, 2018, 25(7):1073-1082.
15
Wang ZB, Hao JX, Meng TG, et al. Transfer of autologous mitochondria from adipose tissue-derived stem cells rescues oocyte quality and infertility in agedmice[J]. Aging, 2017, 9(12):2480-2488.
16
Esfandyari S, Chugh RM, Park HS, et al. Mesenchymal stem cells as a bio organ for treatment of female infertility[J]. Cells, 2020, 9(10):2253. doi: 10.3390/cells9102253.
17
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[J]. Stem Cells Int, 2020, 2020:3249495. doi: 10.1155/2020/3249495.
18
Bao R, Xu P, Wang Y, et al. Bone marrow derived mesenchymal stem cells transplantation rescues premature ovarian insufficiency induced by chemotherapy[J]. Gynecol Endocrinol, 2018, 34(4):320-326.
19
Guo JQ, Gao X, Lin ZJ, et al. BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause[J]. BMC Cell Biol, 2013, 14:18. doi: 10.1186/1471-2121-14-18.
20
Mahla RS. Stem cell applications in regenerative medicine and disease therapeutics[J]. Int J Cell Biol, 2016, 2016:6940283. doi: 10.1155/2016/6940283.
21
Li K, Peng L, Xing Q, et al. Transplantation of hESCs-derived neural progenitor cells alleviates secondary damage of thalamus after focal cerebral infarction in rats[J]. Stem Cells Transl Med, 2023, 16, 12(8): 553-568.
22
Davila JC, Cezar GG, Thiede M, et al. Use and application of stem cells in toxicology[J]. Toxicol Sci, 2004, 79(2):214-223.
23
Yoon SY, Yoon JA, Park M, et al. Recovery of ovarian function by human embryonic stem cell-derived mesenchymal stem cells in cisplatin-induced premature ovarian failure in mice[J]. Stem Cell Res Ther, 2020, 26, 11(1):255. doi: 10.1186/s13287-020-01769-6.
24
Bahrehbar K, Khanjarpoor Malakhond M, Gholami S. Tracking of human embryonic stem cell-derived mesenchymal stem cells in premature ovarian failure model mice[J]. Biochem Biophys Res Commun, 2021, 577:6-11.
25
Bahrehbar K, Gholami S, Nazari Z, et al. Embryonic stem cells-derived mesenchymal stem cells do not differentiate into ovarian cells but improve ovarian function in POF mice[J]. Biochem Biophys Res Commun, 2022, 635:92-98.
26
Shin EY, Kim DS, Lee MJ, et al. Prevention of chemotherapy-induced premature ovarian insufficiency in mice by scaffold-based local delivery of human embryonic stem cell-derived mesenchymal progenitor cells[J]. Stem Cell Res Ther, 2021, 12(1):431-451.
27
Gadkari R, Zhao L, Teklemariam T, et al. Human embryonic stem cell derived-mesenchymal stem cells: an alternative mesenchymal stem cell source for regenerative medicine therapy[J]. Regen Med, 2014, 9(4):453-465.
28
Bahrehbar K, Rezazadeh Valojerdi M, Esfandiari F, et al. Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure[J]. World J Stem Cells, 2020, 12(8):857-878.
29
Anchan R, Gerami-Naini B, Lindsey JS, et al. Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells[J]. PLoS One, 2015, 10(3):e0119275. doi: 10.1371/journal.pone.0119275.
30
Zhang J, Li H, Wu Z, et al. Differentiation of rat iPS cells and ES cells into granulosa cell-like cells[J]. Acta Biochim Biophys Sin (Shanghai), 2013, 45(4):289-295.
31
Pierson Smela MD, Kramme CC, Fortuna PRJ, et al. Directed differentiation of human iPSCs to functional ovarian granulosa-like cells via transcription factor overexpression[J]. Elife, 2023, 12::e83291. doi: 10.7554/eLife.83291.
32
Lu CY, Chen YA, Syu SH, et al. Generation of induced pluripotent stem cell line-NTUHi001-A from a premature ovarian failure patient with Turner's syndrome mosaicism[J]. Stem Cell Res, 2019, 37:101422. doi: 10.1016/j.scr.2019.101422.
33
Liu T, Li Q, Wang S, et al. Transplantation of ovarian granulosa-like cells derived from human induced pluripotent stem cells for the treatment of murine premature ovarian failure[J]. Mol Med Rep, 2016, 13(6):5053-5058.
34
Liu T, Qin W, Huang Y, et al. Induction of estrogen-sensitive epithelial cells derived from human-induced pluripotent stem cells to repair ovarian function in a chemotherapy-induced mouse model of premature ovarian failure[J]. DNA Cell Biol, 2013, 32(12):685-698.
35
Elias KM, Ng NW, Dam KU, et al. Fertility restoration in mice with chemotherapy induced ovarian failure using differentiated iPSCs[J]. EBioMedicine, 2023, 94:104715. doi: 10.1016/j.ebiom.2023.104715.
36
Kanemura H, Go MJ, Shikamura M, et al. Tumorigenicity studies of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration[J]. PLoS One, 2014, 9(1):e85336. doi: 10.1371/journal.pone.0085336.
37
Lee AS, Tang C, Rao MS, et al. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies[J]. Nat Med, 2013, 19(8):998-1004.
38
Gore A, Li Z, Fung HL, et al. Somatic coding mutations in human induced pluripotent stem cells[J]. Nature, 2011, 471(7336):63-67.
39
Park HS, Chugh RM, El Andaloussi A, et al. Human BM-MSC secretome enhances human granulosa cell proliferation and steroidogenesis and restores ovarian function in primary ovarian insufficiency mouse model[J]. Sci Rep, 2021, 11(1):4525. doi: 10.1038/s41598-021-84216-7.
40
Liu J, Zhang H, Zhang Y, et al. Homing and restorative effects of bone marrow-derived mesenchymal stem cells on cisplatin injured ovaries in rats[J]. Mol Cells, 2014, 37(12):865-872.
41
Chen X, Wang Q, Li X, et al. Heat shock pretreatment of mesenchymal stem cells for inhibiting the apoptosis of ovarian granulosa cells enhanced the repair effect on chemotherapy-induced premature ovarian failure[J]. Stem Cell Res Ther, 2018, 9(1):240. doi: 10.1186/s13287-018-0964-4.
42
El-Derany MO, Said RS, El-Demerdash E. Bone marrow-derived mesenchymal stem cells reverse radiotherapy-induced premature ovarian failure: emphasis on signal integration of TGF-β, Wnt/β-catenin and hippo pathways[J]. Stem Cell Rev Rep, 2021, 17(4):1429-1445.
43
Herraiz S, Buigues A, Díaz-García C, et al. Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell infusion[J]. Fertil Steril, 2018, 109(5):908-918.e2.
44
ArefNezhad R, Motedayyen H, Mohammadi A. Therapeutic aspects of mesenchymal stem cell-based cell therapy with a focus on human amniotic epithelial cells in multiple sclerosis: a mechanistic review[J]. Int J Stem Cells, 2021, 14(3):241-251.
45
Zhao YX, Chen SR, Su PP, et al. Using mesenchymal stem cells to treat female infertility: an update on female reproductive diseases[J]. Stem Cells Int, 2019, 2019:9071720. doi: 10.1155/2019/9071720.
46
Takehara Y, Yabuuchi A, Ezoe K, et al. The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function[J]. Lab Invest, 2013, 93(2):181-193.
47
Çil N, Mete GA. The effect of adipose-derived mesenchymal stem cell treatment on mTOR and p-mTOR expression in ovarian damage due to cyclophosphamide[J]. Reprod Toxicol, 2021, 103:71-78.
48
Varaa N, Azandeh S, Khodabandeh Z, et al. Wharton's jelly mesenchymal stem cell: various proto-cols for isolation and differentiation of hepatocyte-like cells; narrative review[J]. Iran J Med Sci, 2019, 44(6):437-448.
49
Kita K, Gauglitz GG, PhanTT, et al. Isolation and characterization of mesenchymal stem cells from the sub-amniotic human umbilical cord lining mem-brane[J]. Stem Cells Dev, 2010, 19(4):491-502.
50
Shen J, Cao D, Sun JL. Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure[J]. World J Stem Cells, 2020, 12(4):277-287.
51
Wang S, Yu L, Sun M, et al. The therapeutic potential of umbilical cord mesenchymal stem cells in mice premature ovarian failure[J]. Biomed Res Int, 2013, 2013:690491. doi: 10.1155/2013/690491.
52
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)[J]. Gynecol Endocrinol, 2021, 37(4):353-357.
53
Jalalie L, Rezaee MA, Rezaie MJ, et al. Human umbilical cord mesenchymal stem cells improve morphometric and histopathologic changes of cyclophosphamide-injured ovarian follicles in mouse model of premature ovarian failure[J]. Acta Histochem, 2021, 123(1):151658. doi: 10.1016/j.acthis.2020.151658.
54
Li J, Mao Q, He J, et al. Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism[J]. Stem Cell Res Ther, 2017, 8(1):55. doi: 10.1186/s13287-017-0514-5.
55
Jiao W, Mi X, Yang Y, et al. Mesenchymal stem cells combined with autocrosslinked hyaluronic acid improve mouse ovarian function by activating the PI3K-AKT pathway in a paracrine manner[J]. Stem Cell Res Ther, 2022, 2, 13(1):49. doi: 10.1186/s13287-022-02724-3.
56
Song D, Zhong Y, Qian C, et al. Human umbilical cord mesenchymal stem cells therapy in cyclophosphamide-induced premature ovarian failure rat model[J]. Biomed Res Int, 2016, 2016:2517514. doi: 10.1155/2016/2517514.
57
Deng T, He J, Yao Q, et al. Human umbilical cord mesenchymal stem cells improve ovarian function in chemotherapy-induced premature ovarian failure mice through inhibiting apoptosis and inflammation via a paracrine mechanism[J]. Reprod Sci, 2021, 28(6):1718-1732.
58
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[J]. Stem Cell Res Ther, 2019, 22, 10(1):214. doi: 10.1186/s13287-019-1313-y.
59
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[J]. Stem Cell Res Ther, 2020, 4, 11(1):49. doi: 10.1186/s13287-019-1537-x.
60
Zhang M, Xie T, Dai W, et al. Umbilical cord mesenchymal stem cells ameliorate premature ovarian insufficiency in rats[J]. Evid Based Complement Alternat Med, 2022, 2022:9228456. doi: 10.1155/2022/9228456.
61
Lv X, Guan C, Li Y, et al. Effects of single and multiple transplantations of human umbilical cord mesenchymal stem cells on the recovery of ovarian function in the treatment of premature ovarian failure in mice[J]. J Ovarian Res, 2021, 14(1):119. doi: 10.1186/s13048-021-00871-4.
62
Silvestris E, Cafforio P, Felici C, et al. Ddx4+ oogonial stem cells in postmenopausal women's ovaries: a controversial, undefined role[J]. Cells, 2019, 28, 8(7):650. doi: 10.3390/cells8070650.
63
Silvestris E, D'Oronzo S, Cafforio P, et al. In vitro generation of oocytes from ovarian stem cells (OSCs): in search of major evidence[J]. Int J Mol Sci, 2019, 20(24):6225. doi: 10.3390/ijms20246225.
64
Silvestris E, Minoia C, Guarini A, et al. Ovarian stem cells (OSCs) from the cryopreserved ovarian cortex: a potential for neo-oogenesis in women with cancer-treatment related infertility: a case report and a review of literature[J]. Curr Issues Mol Biol, 2022, 44(5):2309-2320.
65
Johnson J, Canning J, Kaneko T, et al. Germline stem cells and follicular renewal in the postnatal mammalian ovary[J]. Nature, 2004, 428(6979):145-150.
66
Liu J, Shang D, Xiao Y, et al. Isolation and characterization of string-forming female germline stem cells from ovaries of neonatal mice[J]. J Biol Chem, 2017, 292(39):16003-16013.
67
Adib S, Valojerdi MR. Molecular assessment, characterization, and differentiation of theca stem cells imply the presence of mesenchymal and pluripotent stem cells in sheep ovarian theca layer[J]. Res Vet Sci, 2017, 114:378-387.
68
Dalman A, Totonchi M, Valojerdi MR. Establishment and characterization of human theca stem cells and their differentiation into theca progenitor cells[J]. J Cell Biochem, 2018, 119(12):9853-9865.
69
Stimpfel M, Cerkovnik P, Novakovic S, et al. Putative mesenchymal stem cells isolated from adult human ovaries[J]. J Assist Reprod Genet, 2014, 31(8):959-974.
70
De Coppi P, Bartsch G Jr, Siddiqui MM, et al. Isolation of amniotic stem cell lines with potential for therapy[J]. Nat Biotechnol, 2007, 25(1):100-106.
71
Xiao GY, Liu IH, Cheng CC, et al. Amniotic fluid stem cells prevent follicle atresia and rescue fertility of mice withpremature ovarian failure induced by chemotherapy[J]. PLoS One, 2014, 9(9):e106538. doi: 10.1371/journal.pone.0106538.
72
Liu T, Huang Y, Zhang J, et al. Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model[J]. Stem Cells Dev, 2014, 23 (13):1548-1557.
73
Wang Z, Wang Y, Yang T, et al. Study of the reparative effects of menstrual-derived stem cells on premature ovarian failure in mice[J]. Stem Cell Res Ther, 2017, 8 (1): 11. doi: 10.1186/s13287-016-0458-1.
74
Zhang Q, Bu S, Sun J, et al. Paracrine effects of human amniotic epithelial cells protect against chemotherapy-induced ovarian damage[J]. Stem Cell Res Ther, 2017, 8 (1): 270. doi: 10.1186/s13287-017-0721-0.
75
Ling L, Feng X, Wei T, et al. Human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation improves ovarian function in rats with premature ovarian insufficiency (POI) at least partly through a paracrine mechanism[J]. Stem Cell Res Ther, 2019, 10(1):46. doi: 10.1186/s13287-019-1136-x.
76
Edessy M, Hosni HN, Shady Y, et al. Autologous stem cells therapy, the first baby of idiopathic premature ovarian failure[J]. Acta Medica International, 2016, 3(1):19-23.
77
Igboeli P, El Andaloussi A, Sheikh U, et al. Intraovarian injection of autologous human mesenchymal stem cells increases estrogen production and reduces menopausal symptoms in women with premature ovarian failure: two case reports and a review of the literature[J]. J Med Case Rep, 2020, 14(1):108. doi: 10.1186/s13256-020-02426-5.
78
Mashayekhi M, Mirzadeh E, Chekini Z, et al. Evaluation of safety, feasibility and efficacy of intra-ovarian transplantation of autologous adipose derived mesenchymal stromal cells in idiopathic premature ovarian failure patients: non-randomized clinical trial, phase I, first in human[J]. J Ovarian Res, 2021, 14(1):5. doi: 10.1186/s13048-020-00743-3.
79
Yan L, Wu Y, Li L, et al. Clinical analysis of human umbilical cord mesenchymal stem cell allotransplantation in patients with premature ovarian insufficiency[J]. Cell Prolif, 2020, 53(12):e12938. doi: 10.1111/cpr.12938.
80
Herraiz S, Romeu M, Buigues A, et al. Autologous stem cell ovarian transplantation to increase reproductive potential in patients who are poor responders[J]. Fertil Steril, 2018, 110(3):496-505.e1.
81
Gupta S, Lodha P, Karthick MS, et al. Role of autologous bone marrow-derived stem cell therapy for follicular recruitment in premature ovarian insufficiency: review of literature and a case report of world's first baby with ovarian autologous stem cell therapy in a perimenopausal woman of age 45 year[J]. J Hum Reprod Sci, 2018, 11(2):125-130.
82
Chen H, Wen X, Liu S, et al. Dissecting heterogeneity reveals a unique BAMBIhigh MFGE8high subpopulation of human UC-MSCs[J]. Adv Sci (Weinh), 2022, 10(1):e2202510. doi: 10.1002/advs.202202510.
83
Ding L, Yan G, Wang B, et al. Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility[J]. Sci China Life Sci, 2018, 61(12):1554-1565.
84
Zafardoust S, Kazemnejad S, Darzi M, et al. Intraovarian administration of autologous menstrual blood derived-mesenchymal stromal cells in women with premature ovarian failure[J]. Arch Med Res, 2023, 54(2):135-144.
85
Ling L, Feng X, Wei T, et al. Effects of low-intensity pulsed ultrasound (LIPUS)-pretreated human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation on primary ovarian insufficiency in rats[J]. Stem Cell Res Ther, 2017, 8(1):283-299.
86
Huang Y, Ma Z, Kuang X, et al. Sodium alginate-bioglass-encapsulated hAECs restore ovarian function in premature ovarian failure by stimulating angiogenic factor secretion[J]. Stem Cell Res Ther, 2021, 12(1):223. doi: 10.1186/s13287-021-02280-2.
87
Zhou Y, Zhou J, Xu X, et al. Matrigel/umbilical cord-derived mesenchymal stem cells promote granulosa cell proliferation and ovarian vascularization in a mouse model of premature ovarian failure[J]. Stem Cells Dev, 2021, 30(15):782-796.
88
Zhang S, Zhu D, Li Z, et al. A stem cell-derived ovarian regenerative patch restores ovarian function and rescues fertility in rats with primary ovarian insufficiency[J]. Theranostics, 2021, 11(18):8894-8908.
89
Su J, Ding L, Cheng J, et al. Transplantation of adipose-derived stem cells combined with collagen scaffolds restores ovarian function in a rat model of premature ovarian insufficiency[J]. Hum Reprod, 2016, 31(5):1075-1086.
90
Yang Y, Lei L, Wang S, et al. Transplantation of umbilical cord-derived mesenchymal stem cells on a collagen scaffold improves ovarian function in a premature ovarian failure model of mice[J]. In Vitro Cell Dev Biol Anim, 2019, 55(4):302-311.
91
Zhang J, Yin H, Jiang H, et al. The protective effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles on cisplatin-damaged granulosa cells[J]. Taiwan J Obstet Gynecol, 2020, 59(4):527-533.
92
Sun L, Li D, Song K, et al. Exosomes derived from human umbilical cord mesenchymal stem cells protect against cisplatin-induced ovarian granulosa cell stress and apoptosis in vitro[J]. Sci Rep, 2017, 7(1):2552. doi: 10.1038/s41598-017-02786-x.
93
Yang Z, Du X, Wang C, et al. Therapeutic effects of human umbilical cord mesenchymal stem cell-derived microvesicles on premature ovarian insufficiency in mice[J]. Stem Cell Res Ther, 2019, 10(1):250. doi: 10.1186/s13287-019-1327-5.
94
Sun B, Ma Y, Wang F, et al. miR-644-5p carried by bone mesenchymal stem cell-derived exosomes targets regulation of p53 to inhibit ovarian granulosa cell apoptosis[J]. Stem Cell Res Ther, 2019, 10(1):360. doi: 10.1186/s13287-019-1442-3.
95
Xiao GY, Cheng CC, Chiang YS, et al. Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy[J]. Sci Rep, 2016, 6:23120. doi: 10.1038/srep23120.
96
Li Z, Zhang M, Zheng J, et al. Human umbilical cord mesenchymal stem cell-derived exosomes improve ovarian function and proliferation of premature ovarian insufficiency by regulating the hippo signaling pathway[J]. Front Endocrinol (Lausanne), 2021, 12:1-17.
97
Huang B, Lu J, Ding C, et al. Exosomes derived from human adipose mesenchymal stem cells improve ovary function of premature ovarian insufficiency by targeting SMAD[J]. Stem Cell Res Ther, 2018, 9(1):216. doi: 10.1186/s13287-018-0953-7.
98
Yang M, Lin L, Sha C, et al. Bone marrow mesenchymal stem cell-derived exosomal miR-144-5p improves rat ovarian function after chemotherapy-induced ovarian failure by targeting PTEN[J]. Lab Invest, 2020, 100(3):342-352.
99
Pu X, Zhang L, Zhang P, et al. Human UC-MSC-derived exosomes facilitate ovarian renovation in rats with chemotherapy-induced premature ovarian insufficiency[J]. Front Endocrinol (Lausanne), 2023, 14:1205901. doi: 10.3389/fendo.2023.1205901.
100
Ding C, Zhu L, Shen H, et al. Exosomal miRNA-17-5p derived from human umbilicalcord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7[J]. Stem Cells, 2020, 38(9):1137-1148.
101
Ding C, Qian C, Hou S, et al. Exosomal miRNA-320a is released from hAMSCs and regulates SIRT4 to prevent reactive oxygen species generation in POI[J]. Mol Ther Nucleic Acids, 2020, 21:37-50.
102
Thabet E, Yusuf A, Abdelmonsif DA, et al. Extracellular vesicles miRNA-21: a potential therapeutic tool in premature ovarian dysfunction[J]. Mol Hum Reprod, 2020, 26(12):906-919.
103
Liu M, Qiu Y, Xue Z, et al. Small extracellular vesicles derived from embryonic stem cells restore ovarian function of premature ovarian failure through PI3K/AKT signaling pathway[J]. Stem Cell Res Ther, 2020, 11(1):3. doi: 10.1186/s13287-019-1508-2.
104
Geng Z, Chen H, Zou G, et al. Human amniotic fluid mesenchymal stem cell-derived exosomes inhibit apoptosis in ovarian granulosa cell via miR-369-3p/YAF2/PDCD5/p53 pathway[J]. Oxid Med Cell Longev, 2022, 2022:3695848. doi: 10.1155/2022/3695848.
105
Liu C, Yin H, Jiang H, et al. Extracellular vesicles derived from mesenchymal stem cells recover fertility of premature ovarian insufficiency mice and the effects on their offspring[J]. Cell Transplant, 2020, 29:963689720923575. doi: 10.1177/0963689720923575.
106
Marinaro F, Macías-GarcíaB, Sánchez-Margallo FM, et al. Extracellular vesicles derived from endometrial human mesenchymal stem cells enhance embryo yield and quality in an aged murine model[J]. Biol Reprod, 2019, 100(5):1180-1192.
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