Cell Therapy Facility, The Blood Bank, Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
The Nordic Cochrane Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Neurobiol Dis. 2014 Feb;62:338-53. doi: 10.1016/j.nbd.2013.10.014. Epub 2013 Oct 19.
Traumatic spinal cord injury (SCI) is a devastating event with huge personal and societal costs. A limited number of treatments exist to ameliorate the progressive secondary damage that rapidly follows the primary mechanical impact. Mesenchymal stem or stromal cells (MSCs) have anti-inflammatory and neuroprotective effects and may thus reduce secondary damage after administration. We performed a systematic review with quantitative syntheses to assess the evidence of MSCs versus controls for locomotor recovery in rat models of traumatic SCI, and identified 83 eligible controlled studies comprising a total of 1,568 rats. Between-study heterogeneity was large. Fifty-three studies (64%) were reported as randomised, but only four reported adequate methodologies for randomisation. Forty-eight studies (58%) reported the use of a blinded outcome assessment. A random-effects meta-analysis yielded a difference in behavioural Basso-Beattie-Bresnahan (BBB) locomotor score means of 3.9 (95% confidence interval [CI] 3.2 to 4.7; P<0.001) in favour of MSCs. Trial sequential analysis confirmed the findings of the meta-analyses with the upper monitoring boundary for benefit being crossed by the cumulative Z-curve before reaching the diversity-adjusted required information size. Only time from intervention to last follow-up remained statistically significant after adjustment using multivariate random-effects meta-regression modelling. Lack of other demonstrable explanatory variables could be due to insufficient meta-analytic study power. MSCs would seem to demonstrate a substantial beneficial effect on locomotor recovery in a widely-used animal model of traumatic SCI. However, the animal results should be interpreted with caution concerning the internal and external validity of the studies in relation to the design of future clinical trials.
创伤性脊髓损伤(SCI)是一种具有巨大个人和社会成本的破坏性事件。目前仅有少数治疗方法可以改善原发性机械冲击后迅速发生的进行性继发性损伤。间充质干细胞(MSCs)具有抗炎和神经保护作用,因此在给药后可能会减少继发性损伤。我们进行了一项系统评价和定量综合分析,以评估 MSCs 与对照在创伤性 SCI 大鼠模型中运动功能恢复的证据,并确定了 83 项符合条件的对照研究,共纳入 1568 只大鼠。研究间异质性较大。53 项研究(64%)报告为随机分组,但仅有 4 项报告了充分的随机分组方法。48 项研究(58%)报告了使用盲法结局评估。随机效应荟萃分析得出行为 Basso-Beattie-Bresnahan(BBB)运动评分均值的差异为 3.9(95%置信区间 3.2 至 4.7;P<0.001),有利于 MSCs。试验序贯分析通过累积 Z 曲线在达到多样性调整所需信息量之前越过获益的上监测边界,证实了荟萃分析的结果。使用多变量随机效应荟萃回归模型进行调整后,仅干预到最后随访的时间仍然具有统计学意义。在使用多变量随机效应荟萃回归模型进行调整后,仅干预到最后随访的时间仍然具有统计学意义。缺乏其他可证明的解释变量可能是由于荟萃分析研究的效力不足。MSCs 在广泛使用的创伤性 SCI 动物模型中似乎对运动功能恢复具有显著的有益作用。然而,鉴于未来临床试验的设计,应谨慎解释这些动物研究的内部和外部有效性。