摘要
目的:近年来卵巢早衰呈现年轻化趋势,干细胞治疗已逐渐应用于临床工作。但因干细胞来源广泛,存在于各类组织中,其生物学特征及功能存在一定差异。文章通过比较不同来源的间充质干细胞治疗卵巢早衰动物模型的疗效,为干细胞临床应用提供依据。方法:计算机分别从PubMed、The Cochrane Library、EMbase外文数据库和中国知网、万方、维普、中国生物医学文献服务系统中文数据库中检索间充质干细胞治疗卵巢早衰动物模型实验,检索时限从各数据库建库之日起至2023-12-31。由2名研究者独立筛选文献、提取和分析数据。纳入研究均采用SYRCLE动物实验偏倚风险评估表进行质量评价。主要结局指标:卵泡刺激素、雌二醇、黄体生成素及各级卵泡数;次要结局指标:妊娠率。在评价纳入研究的偏倚风险后使用Stata 17.0软件进行网状Meta分析、绘图和制表。结果:最终纳入24项动物实验研究,文献整体质量为中等质量,包括7种不同来源的间充质干细胞,分别为脐带源性间充质干细胞(UCMSCs)、经血源性间充质干细胞(HuMenSCs)、胎盘源性间充质干细胞(HP-MSCs)、人脐血源性间充质干细胞(HCMNCs)、骨髓源性间充质干细胞(BM-MSCs)、脂肪源性间充质干细胞(AD-MSCs)和羊膜源性间充质干细胞(HA-MSCs)。网状Meta结果分析显示:(1)与空白组相比,各实验组在提高实验动物妊娠率、雌二醇,降低卵泡刺激素、黄体生成素,增加各级卵泡数,减少闭锁卵泡数方面,不同来源的间充质干细胞均有疗效。(2)累计排序曲线下面积图可得出,提高雌二醇水平的疗效排名前3位的为:脐带源性间充质干细胞组(72.7%)>脂肪源性间充质干细胞组(72.6%)>经血源性间充质干细胞组(71.7%);(3)降低卵泡刺激素水平的疗效排名前3位的为:脂肪源性间充质干细胞组(96.3%)>人脐血源性间充质干细胞组(65.4%)>脐带源性间充质干细胞组(63.9%);(4)降低黄体生成素水平的疗效排名前3位的为:脂肪源性间充质干细胞组(100.0%)>脐带源性间充质干细胞组(51.6%)>人脐血源性间充质干细胞组(46.8%);(5)增加原始卵泡数的疗效排名前3位的为:人脐血源性间充质干细胞组(76.3%)>脐带源性间充质干细胞组(75.5%)>经血源性间充质干细胞组(57.5%);(6)增加初级卵泡数的疗效排名前3位的为:脐带源性间充质干细胞组(75.3%)>脂肪源性间充质干细胞组(53.0%)>胎盘源性间充质干细胞组(51.7%);(7)增加次级卵泡数的疗效排名前3位的为:脂肪源性间充质干细胞组(76.1%)>经血源性间充质干细胞组(66.8%)>脐带源性间充质干细胞组(66.5%);(8)减少闭锁卵泡数的疗效排名前3位的为:脂肪源性间充质干细胞组(99.9%)>骨髓源性间充质干细胞组(68.1%)>脐带源性间充质干细胞组(53.4%)。结论:(1)针对卵巢早衰的动物模型,此网状Meta分析结果得出各种干细胞移植治疗均不同程度优于空白组/安慰剂组且疗效相似。(2)综合各结局指标及干细胞的组间比较发现,目前脐带源性间充质干细胞的应用最广泛,脂肪源性间充质干细胞疗效最佳,未来需要更多高质量的临床试验数据进一步验证。
OBJECTIVE:Premature ovarian failure has manifested a trend of younger,and stem cell therapy has been progressively implemented in clinical practice in recent years.Nevertheless,given the extensive range of sources and variegated existence of stem cells in diverse tissues,certain disparities prevail in their biological characteristics and functions.In this paper,the therapeutic efficacies of dissimilar sources of mesenchymal stem cells on animal models of premature ovarian failure were contrasted,with the aim of providing a basis for the clinical application of stem cells.METHODS:The animal model experiments of mesenchymal stem cell therapy for premature ovarian failure were retrieved from PubMed,The Cochrane Library,and EMbase,as well as Chinese databases such as CNKI,WanFang,VIP,and China Biomedical Literature Service.The search period extended from the inception to December 31,2023.Two researchers independently screened the literature,extracted and analyzed the data.The quality of the included studies was evaluated by means of the SYRCLE animal experiment bias risk assessment table.Main outcome measures:Follicle stimulating hormone,estradiol,luteinizing hormone,the quantity of follicles at all levels.Secondary outcome measure:Pregnancy rate.Network meta-analysis,mapping,and tabulation were executed using Stata 17.0 software after assessing the risk of bias in the included studies.RESULTS:Totally 24 animal experiment studies were incorporated,and the overall quality of the literature was mediocre,encompassing 7 distinct sources of mesenchymal stem cells.They were umbilical cord-derived mesenchymal stem cells,menstrual blood-derived mesenchymal stem cells,placenta-derived mesenchymal stem cells,human cord blood-derived mesenchymal stem cells,bone marrow-derived mesenchymal stem cells,adipose-derived mesenchymal stem cells,and amnio-derived mesenchymal stem cells.The network meta-analysis demonstrated that(1)in contrast to the blank group,mesenchymal stem cells from various sources were effective in enhancing the pregnancy rate and estradiol,reducing follicle-stimulating hormone and luteinizing hormone,augmenting the number of follicles at all levels,and diminishing the number of atretic follicles.(2)According to the area map under the cumulative sequencing curve,the three stem cells with the most prominent efficacy in improving estradiol levels were umbilical cord-derived mesenchymal stem cells(72.7%)>adipose-derived mesenchymal stem cells(72.6%)>menstrual blood-derived mesenchymal stem cells(71.7%).(3)The three kinds of stem cells with the highest efficacy in reducing follicle-stimulating hormone levels were the adipose-derived mesenchymal stem cells(96.3%)>human cord blood-derived mesenchymal stem cells(65.4%)>umbilical cord-derived mesenchymal stem cells(63.9%).(4)The three kinds of stem cells with the highest efficacy in reducing luteinizing hormone levels were adipose-derived mesenchymal stem cells(100.0%)>umbilical cord-derived mesenchymal stem cells(51.6%)>human cord blood-derived mesenchymal stem cells(46.8%).(5)The top three kinds of stem cells for increasing the number of primordial follicles were human cord blood-derived mesenchymal stem cells(76.3%)>umbilical cord-derived mesenchymal stem cells(75.5%)>menstrual blood-derived mesenchymal stem cells(57.5%).(6)The top three kinds of stem cells for increasing the number of primary follicles were umbilical cord-derived mesenchymal stem cells(75.3%)>adipose-derived mesenchymal stem cells(53.0%)>the placenta-derived mesenchymal stem cells(51.7%).(7)The top three kinds of stem cells for increasing the number of secondary follicles were adipose-derived mesenchymal stem cells(76.1%)>menstrual blood-derived mesenchymal stem cells(66.8%)>umbilical cord-derived mesenchymal stem cells(66.5%).(8)The top three kinds of stem cells in reducing the number of atretic follicles were adipose-derived mesenchymal stem cells(99.9%)>bone marrow-derived mesenchymal stem cells(68.1%)>umbilical cord-derived mesenchymal stem cells(53.4%).CONCLUSION:(1)For animal models of premature ovarian failure,the results of the network meta-analysis disclosed that various stem cell transplantation treatments were preponderant over the blank or placebo group to varying extents,and the efficacies were comparable.(2)The results indicated that umbilical cord-derived mesenchymal stem cells were the most frequently utilized and adipose-derived mesenchymal stem cells were the most potent.More high-quality experimental study data are requisite in the future for further validation.
作者
李哲
李萍
张超
郭广玲
Li Zhe;Li Ping;Zhang Chao;Guo Guangling(Anti-Aging Center,Affiliated Hospital of Hubei University of Medicine(Taihe Hospital),Shiyan 442000;Evidence-Based Medicine Center,Affiliated Hospital of Hubei University of Medicine(Taihe Hospital),Shiyan 442000,Hubei Province,China)
出处
《中国组织工程研究》
北大核心
2025年第36期7898-7908,共11页
Chinese Journal of Tissue Engineering Research
基金
十堰市科技局科研项目(22Y46)项目负责人:郭广玲。
关键词
干细胞
卵巢早衰
动物实验
网状Meta分析
卵泡数
雌二醇
卵泡刺激素
黄体生成素
stem cells
premature ovarian failure
animal experiments
network meta-analysis
follicular number
estradiol
follicle-stimulating hormone
luteinizing hormone
