间充质干细胞治疗膝骨关节炎的疗效及安全性Meta分析  

The effectiveness and safety of mesenchymal stem cells in the treatment of osteoarthritis:a Meta-analysis of randomized control trials

作　　者：张文正 雷雪枫 涂意辉[1] 薛华明[1] Zhang Wenzheng;Lei Xuefeng;Tu Yihui;Xue Huaming(Department of Joint Surgery,Yangpu Hospital,School of Medicine,Tongji University,Shanghai,200090,China)

机构地区：[1]同济大学医学院同济大学附属杨浦医院骨关节外科,上海200090

出　　处：《中华风湿病学杂志》2024年第5期327-332,I0002,共7页Chinese Journal of Rheumatology

基　　金：上海市科委医学创新研究专项项目(21Y11911600)。

摘　　要：目的系统评价间充质干细胞(MSC)治疗膝骨关节炎(KOA)的治疗效果及安全性。方法系统检索PubMed、OVID平台、Web of Science、中国知网、万方等数据库自建库至2023年5月使用MSC治疗KOA的随机对照试验。按照纳入及排除标准进行文献筛选及数据提取,采用RevMan 5.4软件进行Meta分析,并使用I^(2)进行异质性检验,I^(2)>50%则采用随机效应模型,反之采用固定效应模型。使用倒方差加权法计算合并效应量平均差(MD)及其95%置信区间(CI)。采用Stata 14.0软件进行灵敏度及发表偏倚评估。结果纳入29项随机对照试验,共计1402例患者。在随访12个月时,相比于对照组,MSC组减轻了疼痛[视觉模拟评分(VAS)评分:[MD值(95%CI)=-2.00(-2.67,-1.33),P<0.001];西大略和麦克马斯特大学骨关节炎评分(WOMAC)疼痛评分:[MD值(95%CI)=-4.38(-7.22,-1.55),P<0.001];MSC同样降低了WOMAC僵硬[WOMAC僵硬评分:[MD值(95%CI)=-1.21(-2.32,-0.10),P<0.001];WOMAC关节功能及OA严重程度在12个月时降低,WOMAC评分:[MD值(95%CI)=-9.40(-15.87,-2.93),P<0.001];Lequesne指数评分[MD值(95%CI)=-10.57(-15.89,-5.24),P<0.001]。以上疗效均至少持续4年。磁共振成像评分(WORMS)显示MSC组与对照组之间软骨形成方面差异无统计学意义[MD值(95%CI)=-6.68(-18.45,5.09),P=0.270];亚组分析显示,MSC的组织来源及剂量对骨关节炎疼痛及关节功能的影响差异无统计学意义。而使用WORMS进行亚组分析,发现脂肪来源的MSC对骨关节炎软骨修复最佳[MD值(95%CI)=-30.94,(-43.87,-18.01),P<0.001]。对于不良事件的发生,没有研究报告相关严重不良反应发生,多数发生不良反应为自限性疼痛及不适,如一过性关节肿胀,腰背酸痛等。结论根据目前证据,MSC可能是一种疗效良好且较为安全的骨关节炎治疗方法,其维持疗效时间长达4年。暂没有可靠证据能够解决何种组织来源及注射细胞剂量疗效最佳这一问题,仍需更多高质量的临床试验进Objective To evaluate the effectiveness and safety of mesenchymal stem cells(MSCs)in the treatment of knee osteoarthritis(KOA).Methods The databases PubMed,OVID,Web of Science,CNKI,Wanfang,were systematically searched from inception to May 2023 to collect randomized control trials(RCTs)of MSCs in the treatment of KOA.The literature was selected according to the inclusion and exclusion criteria,and relevant data was extracted.Meta-analysis was conducted using RevMan 5.4 software.Heterogeneity was assessed using the I2 statistic,with the fixed effects model applied when I2 was less than 50%,and the random effects model utilized otherwise.The combined effect size and 95%confidence interval(CI)were calculated using the inverse-variance method.Sensitivity analysis and assessment of publication bias were performed using Stata 14.0 software.Results A total of 29 RCTs involving 1402 participants were included.The outcomes showed that at the 12 month follow-up,MSCs reduced pain[WOMAC pain:MD(95%CI)=-4.38(-7.22,-1.55),P<0.001;VAS:MD(95%CI)=-2.00(-2.67,-1.33),P<0.001].And WOMAC stiffness[WOMAC stiffness:MD(95%CI)=-1.21(-2.32,-0.10),P<0.001];moreover,MSCs reduced KOA severity and Restored joint function,[WOMAC:MD(95%CI)=-9.40(-15.87,-2.93),P<0.001;Lequesne:MD(95%CI)=-10.57(-15.89,-5.24),P<0.001].And the effect lasted for at least 4 years.MRI analysis showed no significant difference between the MSC group and the control group[MD(95%CI)=-6.68(-18.45,5.09),P=0.270].Subgroup analysis showed that there was no significant difference in the effects of the tissue source and dosage of MSC on osteoarthritis pain and joint function.Using WOMRS for subgroup analysis,we found that adipose tissue was the best MSCs source for cartilage repair in osteoarthritis[MD(95%CI)=-30.94(-43.87,-18.01),P<0.001].For the occurrence of adverse events,no study had reported the occurrence of serious adverse events.Most of the adverse events were self-limited pain and discomfort,such as transient joint swelling and back pain.Conclusion Based on current ev

关 键 词：骨关节炎 间充质干细胞 软骨 注射 关节内 

分 类 号：R684.3[医药卫生—骨科学]