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

doi:10.3877/cma.j.issn.2095-1221.2024.04.007

Abstract

Abstract:

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

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.

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References 106

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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

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

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

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

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]

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