中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (25): 4093-4100.doi: 10.12307/2022.419

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

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

石  尧1,韩树峰2,原一桐3,杜若琛3,景志杰3,赵碧春3,张茹鑫3,张玉娟3,王春芳3   

  1. 1山西医科大学,山西省太原市   030001;2山西医科大学第一医院,山西省太原市   030001;3山西医科大学实验动物中心,山西省太原市   030001
  • 收稿日期:2021-03-29 接受日期:2021-05-08 出版日期:2022-09-08 发布日期:2022-01-26
  • 通讯作者: 韩树峰,硕士,教授,主任医师,山西医科大学第一医院,山西省太原市 030001 王春芳,博士,教授,山西医科大学实验动物中心,山西省太原市 030001
  • 作者简介:石尧,男,山西省临汾市人,汉族,1993年生,山西医科大学在读硕士。
  • 基金资助:
    国家自然科学青年基金(82001326),项目负责人:原一桐;山西省自然科学基金(201801D121212),项目负责人:王春芳;山西省自然科学基金(201901D111384),项目参与人:王春芳,原一桐;山西省自然科学基金(201901D211319),项目负责人:原一桐;山西省重点社会发展项目(201803D31068)项目负责人:王春芳;山西省高等学校科技创新项目(2019L0445),项目负责人:原一桐;山西省高等学校科技创新项目(2019L0418),项目负责人:杜若琛

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

Shi Yao1, Han Shufeng2, Yuan Yitong3, Du Ruochen3, Jing Zhijie3, Zhao Bichun3, Zhang Ruxin3, Zhang Yujuan3, Wang Chunfang3   

  1. 1Shanxi Medical University, Taiyuan 030001, Shanxi Province, China; 2First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China; 3Experimental Animal Center of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Received:2021-03-29 Accepted:2021-05-08 Online:2022-09-08 Published:2022-01-26
  • Contact: Han Shufeng, Master, Professor, Chief physician, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China Wang Chunfang, PhD, Professor, Experimental Animal Center of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • About author:Shi Yao, Master candidate, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Supported by:
    the National Natural Science Youth Foundation, No. 82001326 (to YYT); Natural Science Foundation of Shanxi Province, No. 201801D121212  (to WCF), No. 201901D111384 (to WCF, YYT), No. 201901D211319 (to YYT); Shanxi Provincial Key Social Development Project, No. 201803D31068 (to WCF); Science and Technology Innovation Project of Colleges and Universities in Shanxi Province, No. 2019L0445 (to YYT), No. 2019L0418 (to DRC)

摘要:

文题释义:
脊髓损伤:脊髓损伤是脊柱骨折和/或脱位所造成的严重并发症,由于椎体的移位或碎骨片突入椎管内,使脊髓或马尾神经产生不同程度的损伤。胸腰段脊髓损伤使下肢的感觉和运动产生障碍,称为截瘫;而颈段脊髓损伤后,双上肢也有神经功能障碍,为四肢瘫痪,称为四肢瘫。
Meta分析:也称为“荟萃分析”,是运用定量方法去概括(总结)多个研究结果的系统评价;是文献评价中,将若干个研究结果合并成一个单独数字估计的统计学方法。

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 < 0.000 01)、AIS分级改善率(RR=2.26,95%CI:1.40-3.65,P=0.000 8)、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 < 0.000 01),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。

https://orcid.org/0000-0002-0681-1950 (石尧)

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


关键词: 脊髓损伤, 干细胞治疗, 间充质干细胞, 人脐带间充质干细胞, ASIA评分, AIS分级, 日常生活能力评分, Meta分析

Abstract: 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 < 0.000 01), the improvement rate of AIS grading (RR=2.26, 95%CI:1.40-3.65, P=0.000 8), 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 < 0.000 01), 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.

Key words: spinal cord injury, stem cell therapy, mesenchymal stem cells, human umbilical cord mesenchymal stem cells, ASIA score, AIS classification, activity of daily living scale, meta-analysis

中图分类号: