中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (5): 815-825.doi: 10.4103/1673-5374.206653

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干细胞移植修复脊髓损伤：临床有效性和安全性的meta分析

  

  • 收稿日期:2017-03-09 出版日期:2017-05-15 发布日期:2017-05-15
  • 基金资助:

    国家自然科学基金(81273775)

Stem cell transplantation for spinal cord injury: a meta-analysis of treatment effectiveness and safety

Xiao Fan1, Jin-zhao Wang1, Xiao-min Lin1, Li Zhang1, 2   

  1. 1 Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China; 2 Xiamen Medical College, Xiamen, Fujian Province, China
  • Received:2017-03-09 Online:2017-05-15 Published:2017-05-15
  • Contact: Li Zhang, M.D.,ZhangLiL626@163.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81273775.

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摘要：

 

目的：评价干细胞移植治疗脊髓损伤的临床有效性和安全性。
资料来源：计算机检索PubMed、EMBASE、Cochrane、中国知网、维普、万方及中国生物医学文献数据库中有关干细胞移植治疗脊髓损伤的临床随机对照试验，检索时间自数据库建立时至2016年7月。
资料选择：选择干细胞移植和康复训练治疗脊髓损伤的随机对照临床试验。纳入标准：①脊髓损伤患者神经分级诊断采用美国脊髓损伤协会标准；②脊髓损伤患者只接受干细胞移植或干细胞移植联合康复治疗；③结局指标包括脊髓损伤患者运动功能评分、感觉功能评分、日常生活能力评分、排尿功能、损伤严重程度和不良事件的1条或多条；④排除病例为伴有其他并发症的研究、未能找到全文的研究以及动物实验。采用Cochrane风险偏倚评价工具对纳入研究试验的质量进行评价，采用RevMan5.3版本软件进行统计分析。
结局评价指标：美国脊髓损伤协会损伤分级运动评分、轻触觉评分、刺觉评分、损伤评级改善率、日常生活能力评分、残留尿量和不良事件。
结果：共纳入10项随机对照试验，脊髓损伤患者共377例。总体评价试验研究质量相对不高，其中4项研究未详细说明随机序列产生的方法，2项研究未详细说明是否对评价者实施盲法，2项研究未对评价者实施盲法，1项研究未详细说明病例脱落情况，4项研究存在选择性报告情况。与康复治疗相比，干细胞移植可显著提高脊髓损伤患者的下肢轻触觉评分(OR=3.43, 95%Cl：0.01-6.86, P=0.05)，下肢刺觉评分(OR=3.93, 95%Cl：0.74-7.12，P=0.02)，AIS评级改善率(RR=2.95, 95%Cl：1.64 -5.29, P=0.0003)，显著降低脊髓损伤患者的残留尿量(OR= -8.10, 95%Cl：-15.09- -1.10，P=0.02)，但干细胞移植对脊髓损伤患者的运动功能评分(OR=1.89, 95%Cl：-0.25-4.03, P=0.08)和ADL评分(OR=1.12，95%Cl：-1.17-4.04，P=0.45)无明显改善。此外，干细胞移植治疗可造成一些轻微的不良反应(RR=14.49, 95%Cl：5.34-34.08, P ＜0.00001)，但均可在短时间内缓解。

结论：干细胞移植治疗脊髓损伤虽然可出现一些轻微的、暂时性的不良反应，但安全性较好；可改善脊髓损伤患者的感觉功能和膀胱功能，其原因可能与干细胞移植后移植的干细胞可促进脊髓修复和轴突再髓鞘化有关。作者认为仍需要多中心、大样本、长期随访的临床随机对照试验来进一步验证干细胞移植治疗脊髓损伤的有效性。

ORCID：0000-0003-1034-1821(Li Zhang)

关键词: 神经再生, 脊髓损伤, 干细胞, 细胞移植, 骨髓间充质干细胞, 脐带血干细胞, 神经干细胞, 人类胚胎干细胞, 脊髓损伤, 截瘫, Meta分析, 系统综述

Abstract:

OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of stem cell transplantation for spinal cord injury (SCI).
DATA SOURCES: PubMed, EMBASE, Cochrane, China National Knowledge Infrastructure, China Science and Technology Journal, Wanfang, and SinoMed databases were systematically searched by computer to select clinical randomized controlled trials using stem cell transplantation to treat SCI, published between each database initiation and July 2016.
DATA SELECTION: Randomized controlled trials comparing stem cell transplantation with rehabilitation treatment for patients with SCI. Inclusion criteria: (1) Patients with SCI diagnosed according to the American Spinal Injury Association (ASIA) International standards for neurological classification of SCI; (2) patients with SCI who received only stem cell transplantation therapy or stem cell transplantation combined with rehabilitation therapy; (3) one or more of the following outcomes reported: outcomes concerning neurological function including sensory function and locomotor function, activities of daily living, urination functions, and severity of SCI or adverse effects. Studies comprising patients with complications, without full-text, and preclinical animal models were excluded. Quality of the included studies was evaluated using the Cochrane risk of bias assessment tool and RevMan V5.3 software, provided by the Cochrane Collaboration, was used to perform statistical analysis.
OUTCOME MEASURES: ASIA motor score, ASIA light touch score, ASIA pinprick score, ASIA impairment scale grading improvement rate, activities of daily living score, residual urine volume, and adverse events.
RESULTS: Ten studies comprising 377 patients were included in the analysis and the overall risk of bias was relatively low level. Four studies did not detail how random sequences were generated, two studies did not clearly state the blinding outcome assessment, two studies lacked blinding outcome assessment, one study lacked follow-up information, and four studies carried out selective reporting. Compared with rehabilitation therapy, stem cell transplantation significantly increased the lower limb light touch score (odds ratio (OR) = 3.43, 95% confidence interval (CI): 0.01 – 6.86, P = 0.05), lower limb pinprick score (OR = 3.93, 95%CI: 0.74 – 7.12, P = 0.02), ASI grading rate (relative risk (RR) = 2.95, 95%CI: 1.64 – 5.29, P = 0.0003), and notably reduced residual urine volume (OR = –8.10, 95%CI: –15.09 to –1.10, P = 0.02). However, stem cell transplantation did not significantly improve motor score (OR = 1.89, 95%CI: –0.25 to 4.03, P = 0.08) or activities of daily living score (OR = 1.12, 95%CI: –1.17 to 4.04, P = 0.45). Furthermore, stem cell transplantation caused a high rate of mild adverse effects (RR = 14.49, 95%CI: 5.34 – 34.08, P < 0.00001); however, these were alleviated in a short time.
CONCLUSION: Stem cell transplantation was determined to be an efficient and safe treatment for SCI and simultaneously improved sensory and bladder functions. Although associated minor and temporary adverse effects were observed with transplanted stem cells, spinal cord repair and axon remyelination were apparent. More randomized controlled trials with larger sample sizes and longer follow-up times are needed to further validate the effectiveness of stem cell transplantation in the treatment of SCI.

Key words: nerve regeneration, spinal cord injury, stem cells, cell transplantation, bone marrow mesenchymal stem cells, umbilical cord blood stem cells, neural stem cells, human embryonic stem cells, paraplegia, meta- analysis, neural regeneration