人脐带间充质干细胞治疗脊髓损伤有效性与安全性的Meta分析

Efficacy and safety of human umbilical cord mesenchymal stem cells in the treatment of spinal cord injury:a meta-analysis

目的:目前脊髓损伤仍缺乏十分有效的治疗手段,细胞治疗可能是一种很有前景的治疗手段,其中人脐带间充质干细胞由于其具有易获取、低成本、伦理争议少和免疫原性低等优点受到广泛关注。但目前临床上并没有大范围使用人脐带间充质干细胞,对其有效性和安全性还有争议。文章使用Meta分析来评价人脐带间充质干细胞治疗脊髓损伤的有效性和安全性。方法:应用计算机检索英文数据库(PubMed、Web of Science、Cochrane、EMbase)和中文数据库(中国知网、万方医学网和维普数据库),搜集人脐带间充质干细胞治疗脊髓损伤的临床研究文献,检索时间为各数据库建库至2021年4月。由2位研究人员独立阅读纳入文献、提取资料和评价质量,随机对照试验使用改良Jadad评分量表对纳入文献进行评分,并使用Cochrane风险偏倚评估工具进行偏倚风险评估,队列研究采用NOS量表进行评价,使用RevMan 5.3软件进行Meta分析。结果:共纳入10篇文献,370例患者,包括6篇随机对照试验,4篇队列研究,文献总体质量较高。Meta分析结果显示:①人脐带间充质干细胞移植组的ASIA感觉功能评分(MD=5.20,95%CI:3.50-6.90,P<0.00001)、AIS分级改善率(RR=2.26,95%CI:1.40-3.65,P=0.0008)、日常生活能力评分(Barthel指数)(MD=5.12,95%CI:1.04-9.20,P=0.01)均高于对照组;②人脐带间充质干细胞移植组在ASIA运动功能评分(MD=3.48,95%CI:-0.14-7.10,P=0.06)、ASIA感觉功能评分中细化的针刺觉(MD=7.58,95%CI:-0.44-15.59,P=0.06)、轻触觉(MD=7.67,95%CI:-0.42-15.77,P=0.06)评分方面,与对照组相比差异无显著性意义;③敏感性分析结果显示,在人脐带间充质干细胞移植组ASIA运动功能评分高于对照组(MD=6.14,95%CI:4.46-7.81,P<0.00001),在日常生活能力评分方面,结论与之前保持一致。纳入的10篇文献中,均报道未有严重不良反应发生,但是个别病例存在轻微的不良反应,经对症治疗后均消失。结论:现有的临床证据表明,人脐带间充质干细胞治疗脊髓损伤安全有效,患者的感觉和运动功能以及日常生活能力可得到显著改善。

OBJECTIVE:There is still a lack of effective treatments for spinal cord injury.Cell therapy could be a promising treatment method,in which human umbilical cord mesenchymal stem cells have received wide attention,because of its easy availability,low cost,less ethical issues,and low immunogenicity.At present,it has not been widely used in clinical practice,and its effectiveness and safety are still controversial.A meta-analysis was used to evaluate the efficacy and safety of human umbilical cord mesenchymal stem cells in the treatment of spinal cord injury.METHODS:We searched English databases(PubMed,Web of Science,Cochrane,and EMbase)and Chinese databases(CNKI,Wanfang Medical Network,and VIP),and collected clinical articles on human umbilical cord mesenchymal stem cells in the treatment of spinal cord injury.The retrieval period was from the establishment of the database to April 2021.Two investigators independently read the included studies,extracted the data,and assessed the quality.The randomized controlled trials were scored using the modified Jadad scoring scale,and the Cochrane risk bias assessment tool was used to assess the risk of bias.The cohort studies were evaluated using the NOS scale.Meta-analysis was performed using RevMan5.3 software.RESULTS:A total of 10 studies involving 370 patients,containing 6 randomized controlled trials and 4 cohort studies,were included.The overall quality of the studies was high.Results of the meta-analysis showed that(1)the ASIA sensory function score(MD=5.20,95%CI:3.50-6.90,P<0.00001),the improvement rate of AIS grading(RR=2.26,95%CI:1.40-3.65,P=0.0008),and the Barthel index(MD=5.12,95%CI:1.04-9.20,P=0.01)were higher in the human umbilical cord mesenchymal stem cell treatment group than those in the control group.(2)Compared with the control group,there was no significant difference in ASIA motor function score(MD=3.48,95%CI:-0.14-7.10,P=0.06),ASIA pinprick sensation score(MD=7.58,95%CI:-0.44-15.59,P=0.06)and ASIA light touch score(MD=7.67,95%CI:-0.42-15.77,P=0.06)in the human umbilical cord mesenchymal stem cell treatment group.(3)Sensitivity analysis showed that the ASIA motor function score was higher in the human umbilical cord mesenchymal stem cell treatment group than that in the control group(MD=6.14,95%CI:4.46-7.81,P<0.00001),and the results remained consistent with the previous one for the activities of daily living.In the 10 included articles,no serious adverse reactions were reported,but minor adverse reactions did exist and disappeared after symptomatic treatment.CONCLUSION:The available clinical evidence shows that human umbilical cord mesenchymal stem cells are safe and effective in the treatment of spinal cord injury,with significant improvement in patients’sensory and motor functions as well as their activity of daily living.