中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (4): 748-758.doi: 10.4103/1673-5374.266915

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

神经干细胞移植治疗脊髓挫伤大鼠运动功能的效果：一项Meta分析

  

  • 出版日期:2020-04-15 发布日期:2020-05-29
  • 基金资助:

    国家自然科学基金项目(81171147)，江苏省卫生厅“重点医学人才强威计划”(ZDRCA2016010)，江苏省卫生厅“兴卫计划”重点人才医学研究基金（RC201156），江苏省医学重点学科（XK201117）

Effects of neural stem cell transplantation on the motor function of rats with contusion spinal cord injuries: a meta-analysis

Kai Qian1, Tuo-Ye Xu1, Xi Wang2, Tao Ma1, 3, Kai-Xin Zhang1, 4, Kun Yang1, 5, Teng-Da Qian1, 6, Jing Shi1, Li-Xin Li1, Zheng Wang7   

  1. 1 Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
    2 Department of Intensive Care Unit, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
    3 Department of Neurosurgery, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
    4 Department of Neurosurgery, Huangshan City People’s Hospital, Huangshan, Anhui Province, China
    5 Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, China
    6 Department of Neurosurgery, Jintan Hospital Affiliated to Jiangsu University, Jintan, Jiangsu Province, China
    7 Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
  • Online:2020-04-15 Published:2020-05-29
  • Contact: Li-Xin Li,lilixin2@hotmail.com; Zheng Wang,wangzheng5705@sina.com.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, No. 81171147, “Key Medical Talents of Qiangwei Project” Research Foundation of Health Department of Jiangsu Province of China, No. ZDRCA2016010, “Xingwei Project” Key Personal Medical Research Foundation of Health Department of Jiangsu Province of China, No. RC201156, and Jiangsu Provincial Key Discipline of Medicine of China, No. XK201117 (all to LXL).

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摘要：

目的：评估神经干细胞移植治疗脊髓挫伤后运动功能恢复的效果。

资料来源：在Pubmed，Embase和Cochrane数据库检索建库到2018年9月收录脊髓挫伤大鼠经神经干细胞移植治疗的研究，并以Stata 14.0分析提取的数据。

资料选择：选择以神经干细胞移植治疗脊髓挫伤大鼠模型的研究，且大鼠的运动功能是以BBB评分评价的。同时排除随访时间不足4周且缺乏对照组的研究。

结局评价指标：通过BBB评分评价大鼠运动功能的恢复效果。

结果：通过检索数据库获得1756篇文献，只有30篇符合纳入排除标准，在这30篇文献中共含有37项动物实验。Meta分析结果显示，移植神经干细胞可一定程度促进脊髓挫伤大鼠运动功能的恢复（合并SMD = 0.73，95％CI：0.47-1.00，P <0.001）。从不同供体物种（大鼠：SMD = 0.74，95％CI：0.36-1.13；人：SMD = 0.78，95％CI：0.31-1.25）、供体年龄（胎儿：SMD = 0.67，95％CI：0.43 -0.92；成人：SMD = 0.86，95％CI：0.50-1.22）和组织来源（脑源性：SMD = 0.59，95％CI：0.27-0.91；脊髓来源：SMD = 0.51，95％CI： 0.22-0.79）获得的神经干细胞对运动功能恢复的效果接近，但成人诱导多能干细胞衍生的神经干细胞对促进运动功能恢复没有明显的效果。此外，移植较高剂量的神经干细胞(SMD = 0.62，95% CI: 0.19–1.05)或同步使用免疫抑制剂（SMD = 0.45，95％CI：0.21-0.70）不会获得更好的运动功能恢复。然而在损伤后较短时间进行神经干细胞移植可以获得较好的效果（急性：SMD = 1.22，95％CI：0.81-1.63；亚急性：SMD = 0.75，95％CI：0.42-1.09），且神经干细胞慢性期移植不能明显改善运功功能（SMD = 0.25，95％CI：-0.16-0.65）。

结论：单独神经干细胞移植是治疗脊髓挫伤的一种积极但疗效有限的方法。

orcid: 0000-0001-9114-0356 (Zheng Wang)

关键词: meta分析, 脊髓损伤, 脊髓挫伤, 神经干细胞, 细胞移植, 神经干细胞移植, 大鼠模型, 运动功能恢复, BBB评分, 神经再生

Abstract:

Objective: To judge the efficacies of neural stem cell (NSC) transplantation on functional recovery following contusion spinal cord injuries (SCIs).

Data sources: Studies in which NSCs were transplanted into a clinically relevant, standardized rat model of contusion SCI were identified by searching the PubMed, Embase and Cochrane databases, and the extracted data were analyzed by Stata 14.0.

Data selection: Inclusion criteria were that NSCs were used in in vivo animal studies to treat contusion SCIs and that behavioral assessment of locomotor functional recovery was performed using the Basso, Beattie, and Bresnahan lo-comotor rating scale. Exclusion criteria included a follow-up of less than 4 weeks and the lack of control groups.

Outcome measures: The restoration of motor function was assessed by the Basso, Beattie, and Bresnahan locomotor rating scale.

Results: We identified 1756 non-duplicated papers by searching the aforementioned electronic databases, and 30 full-text articles met the inclusion criteria. A total of 37 studies reported in the 30 articles were included in the meta-analysis. The meta-analysis results showed that transplanted NSCs could improve the motor function recovery of rats following contusion SCIs, to a moderate extent (pooled standardized mean difference (SMD) = 0.73; 95% confidence interval (CI): 0.47–1.00; P < 0.001). NSCs obtained from different donor species (rat: SMD = 0.74; 95% CI: 0.36–1.13; human: SMD = 0.78; 95% CI: 0.31–1.25), at different donor ages (fetal: SMD = 0.67; 95% CI: 0.43–0.92; adult: SMD = 0.86; 95% CI: 0.50–1.22) and from different origins (brain-derived: SMD = 0.59; 95% CI: 0.27–0.91; spinal cord-derived: SMD = 0.51; 95% CI: 0.22–0.79) had similar efficacies on improved functional recovery; however, adult induced pluripotent stem cell-derived NSCs showed no significant efficacies. Furthermore, the use of higher doses of transplanted NSCs or the administration of immunosuppressive agents did not promote better locomotor function recovery (SMD = 0.45; 95% CI: 0.21–0.70). However, shorter periods between the contusion induction and the NSC transplantation showed slightly higher efficacies (acute: SMD = 1.22; 95% CI: 0.81–1.63; subacute: SMD = 0.75; 95% CI: 0.42–1.09). For chronic injuries, NSC implantation did not significantly improve functional recovery (SMD = 0.25; 95% CI: –0.16 to 0.65).

Conclusion: NSC transplantation alone appears to be a positive yet limited method for the treatment of contusion SCIs.

Key words: Basso, Beattie, and Bresnahan locomotor rating scale, cell transplantation, meta-analysis, motor functional recovery, neural regeneration, neural stem cell, neural stem cell transplantation, rat model, spinal contusion, spinal cord injury