中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (29): 4748-4756.doi: 10.3969/j.issn.2095-4344.2017.29.026

• 干细胞循证医学 evidence-based medicine of stem cells • 上一篇    

干细胞移植治疗脊髓损伤系统评价及不同移植途径疗效比较的网状Meta分析

刘 盈，刘楚繁，张慧婷，石 叶，兰 姗，唐玲玲，艾金伟，裴 斌   

  1. 湖北医药学院附属襄阳医院循证医学中心，湖北省襄阳市 442000
  • 出版日期:2017-10-18 发布日期:2017-11-08
  • 通讯作者: 裴斌，硕士生导师，主任医师，教授，湖北医药学院附属襄阳医院循证医学中心，湖北襄阳 442000
  • 作者简介:刘盈，女，1973年生，湖北省襄阳市人，汉族，硕士，副主任护师，主要从事循证医学、创伤护理研究。 并列第一作者：刘楚繁，女，1995年生，湖北省襄阳市人，汉族，本科在读，主要从事循证医学研究。
  • 基金资助:

    湖北省卫生计生西医类2015-2016年度一般项目(WJ2015MB187)；湖北医药学院教研重点项目(2015025)；襄阳市科技计划项目(2010GG3A21)

A systematic review of stem cells in treatment of spinal cord injury and a network Meta-analysis of the therapeutic effects via different transplantation ways

Liu Ying, Liu Chu-fan, Zhang Hui-ting, Shi Ye, Lan Shan, Tang Ling-ling, Ai Jin-wei, Pei Bin   

  1. Evidence-Based Medicine Center, Hubei University of Medicine, Xiangyang 442000, Hubei Province, China
  • Online:2017-10-18 Published:2017-11-08
  • Contact: Pei Bin, Master’s supervisor, Chief physician, Professor, Evidence-Based Medicine Center, Hubei University of Medicine, Xiangyang 442000, Hubei Province, China
  • About author:Liu Ying, Master, Associate chief nurse, Evidence-Based Medicine Center, Hubei University of Medicine, Xiangyang 442000, Hubei Province, China; Liu Chu-fan, Evidence-Based Medicine Center, Hubei University of Medicine, Xiangyang 442000, Hubei Province, China Liu Ying and Liu Chu-fan contributed equally to this work.
  • Supported by:

    the General Program for Western Medicine in 2015-2016 Hubei Health and Family Planning, No. WJ2015MB187; the Teaching and Research Project of Hubei University of Medicine, No. 2015025; the Scientific Plan Project of Xiangyang City, No. 2010GG3A21

PDF

199

摘要：

文题释义：
干细胞移植治疗脊髓损伤的可能机制：干细胞具有较强的迁移能力，定植于脊髓损伤部位。在脊髓损伤局部微环境下，可分化为神经元、胶质细胞及细胞外基质，从而起到填补、替代作用，并可分化为神经突触，并使其发生髓鞘化，重建神经回路。干细胞还通过分泌多种神经营养因子、细胞因子和趋化因子等，以减轻炎症反应，改善脊髓局部微环境，减小继发损伤，保护残存的神经元。此外，干细胞还具有免疫调节作用，可抑制抗原呈递细胞、T淋巴细胞和B 淋巴细胞等多种免疫细胞活性，并抑制树突状细胞诱导的淋巴细胞增殖，减少损伤部位瘢痕形成，减弱神经再生及神经回路建立的物理屏障。

摘要
背景：干细胞移植已被用于脊髓损伤临床治疗，但其安全性和有效性的研究结论存在争议。干细胞移植途径有多种，何种移植途径疗效更佳，现尚无定论。
目的：系统评价干细胞治疗脊髓损伤的安全性和有效性，比较不同干细胞移植途径的疗效差异。
方法：应用计算机检索 PubMed、The Cochrane Library(2016年第4期)、Embase、CNKI、CBM、VIP及Wan-Fang Data数据库，设置截止日期为2016-05-13，收集所有关于干细胞移植治疗脊髓损伤的临床随机对照试验。筛选文献、提取数据，并行文献质量评价后，运用Stata13.0和Gemtc0.14.3软件进行统计分析。
结果与结论：纳入10个临床随机对照试验，合计脊髓损伤患者546例，其中干细胞治疗组294例，康复理疗组252例。Meta分析结果显示，干细胞移植治疗组在增加患者ASIA运动功能评分、ASIA感觉功能评分、生活能力评分及减小膀胱残余尿量方面优于康复理疗组(P < 0.05)。干细胞治疗脊髓损伤出现发热、腹胀、头痛、下肢麻木及脑膜刺激征的概率分别为14%、7%、7%、8%、7%。网状Meta分析结果发现：干细胞蛛网膜下腔注射、静脉注射及病灶内注射3种移植途径在ASIA运动功能评分、ASIA感觉功能评分、生活能力评分及并发症率方面差异比较均无显著性意义；与康复理疗组比较，仅干细胞蛛网膜下腔注射可改善ASIA运动及感觉功能评分[MD=9.77，95%CI(0.26，21.46)；MD=25.79，95%CI(10.07，45.27)]。结果表明，蛛网膜下腔注射可能为较理想的干细胞移植途径。受纳入研究限制，研究结论需开展大量高质量临床随机对照试验予以证实；此外，干细胞治疗脊髓损伤的远期安全性和有效性，以及对不同ASIA病情分级、不同干细胞类型和不同移植时间的疗效有待于进一步研究。

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程
ORCID: 0000-0002-4406-6816(刘盈)

关键词: 干细胞, 移植, 脊髓损伤, 移植, 康复理疗, 移植途径, 安全性, 有效性, 系统评价, 网状Meta分析

Abstract:

BACKGROUND: Stem cell transplantation has been used in the clinical treatment of spinal cord injury. However, the efficacy and safety are still controversial. Although there are many approaches for stem cell transplantation, which one is better is unclear as yet. 
OBJECTIVE: To systematically evaluate the efficacy and safety of stem cell transplantation for spinal cord injury, and to compare the therapeutic difference in stem cell transplantation via different approaches. 
METHODS: A computer-based online search was conducted in PubMed, The Cochrane Library (Issue 4, 2016), Embase, CNKI, VIP, CBM, and Wan-Fang databases up to May 13, 2016 to screen the relevant randomized clinical controlled trials of stem cells in the treatment of spinal cord injury. Two reviewers independently selected the studies, extracted information, and assessed the quality of included trials. Data extracted from eligible studies was pooled and meta-analyzed using Stata13.1 and Gemtc0.14.3 software.
RESULTS AND CONCLUSION: A total of 10 randomized controlled trials involving 546 patients (294 in stem cells group and 252 in rehabilitation treatment group) were included. The results of meta-analysis showed that stem cell transplantation had an advantage over rehabilitation treatment in increasing American Spinal Cord Injury Association (ASIA) motor score, ASIA sensory score, Barthel Index, and decreasing the bladder residual urine volume. The incidence of low fever, abdominal distension, headache, lower limb numbness, and meningeal irritation was 14%, 7%, 7%, 8%, and 7%, respectively. Taking the rehabilitation treatment as a common reference, the results of the network meta-analysis showed that there were no significant differences in ASIA motor score, ASIA sensory score, Barthel Index, and incidence of complications among subarachnoid injection, intravenous injection, and intralesional injection. Compared with the rehabilitation treatment, only stem cell transplantation via subarachnoid injection had significant differences in ASIA motor score [MD=9.77, 95%CI (0.26, 21.46)], and ASIA sensory score [MD=25.79, 95%CI (10.07, 45.27)]. To conclude, the stem cells transplantation via subarachnoid injection is considered the most effective transplantation method. Due to the limitations of the included studies, more high-quality randomized controlled trials are required to verify the above conclusion. In addition, future studies should focus on the long-term efficacy and safety of stem cell transplantation in the treatment of spinal cord injury, and should investigate the clinical effects on spinal cord injury with different ASIA grades, types of stem cells, and transplantation time.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Stem Cells, Spinal Cord Injuries, Transplantation, Computer Systems, Meta-analysis, Tissue Engineering

中图分类号: