脊髓损伤后神经干细胞移植的时机是否会影响动物模型的结果？
Does timing of transplantation of neural stem cells following spinal cord injury affect outcomes in an animal model?
作者信息
Cheng Ivan, Park Don Y, Mayle Robert E, Githens Michael, Smith Robert L, Park Howard Y, Hu Serena S, Alamin Todd F, Wood Kirkham B, Kharazi Alexander I
机构信息
Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, CA, USA.
Department of Orthopaedic Surgery, University of California Los Angeles, Santa Monica, CA, USA.
出版信息
J Spine Surg. 2017 Dec;3(4):567-571. doi: 10.21037/jss.2017.10.06.
BACKGROUND
We previously reported that functional recovery of rats with spinal cord contusions can occur after acute transplantation of neural stem cells distal to the site of injury. To investigate the effects of timing of administration of human neural stem cell (hNSC) distal to the site of spinal cord injury on functional outcomes in an animal model.
METHODS
Thirty-six adult female Long-Evans hooded rats were randomized into three experimental and three control groups with six animals in each group. The T10 level was exposed via posterior laminectomy, and a moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor (MASCIS, W.M. Keck Center for Collaborative Neuroscience, Piscataway, NJ, USA). The animals received either an intrathecal injection of hNSCs or control media through a separate distal laminotomy immediately, one week or four weeks after the induced spinal cord injury. Observers were blinded to the interventions. Functional assessment was measured immediately after injury and weekly using the Basso, Beattie, Bresnahan (BBB) locomotor rating score.
RESULTS
A statistically significant functional improvement was seen in all three time groups when compared to their controls (acute, mean 9.2 4.5, P=0.016; subacute, mean 11.1 6.8, P=0.042; chronic, mean 11.3 5.8, P=0.035). Although there was no significant difference in the final BBB scores comparing the groups that received hNSCs, the group which achieved the greatest improvement from the time of cell injection was the subacute group (+10.3) and was significantly greater than the chronic group (+5.1, P=0.02).
CONCLUSIONS
The distal intrathecal transplantation of hNSCs into the contused spinal cord of a rat led to significant functional recovery of the spinal cord when injected in the acute, subacute and chronic phases of spinal cord injury (SCI), although the greatest gains appeared to be in the subacute timing group.
背景
我们之前报道过，在损伤部位远端急性移植神经干细胞后，脊髓挫伤大鼠可实现功能恢复。为了研究在脊髓损伤部位远端给予人神经干细胞（hNSC）的时间对动物模型功能结局的影响。
方法
将36只成年雌性Long-Evans有帽大鼠随机分为三个实验组和三个对照组，每组6只动物。通过后路椎板切除术暴露T10水平，并使用多中心动物脊髓损伤研究撞击器（MASCIS，美国新泽西州皮斯卡塔韦市W.M. 凯克协作神经科学中心）造成中度脊髓挫伤。在脊髓损伤后立即、1周或4周，通过单独的远端椎板切开术，对动物进行鞘内注射hNSCs或对照培养基。观察者对干预措施不知情。在损伤后立即以及每周使用Basso、Beattie、Bresnahan（BBB）运动评分进行功能评估。
结果
与各自的对照组相比，所有三个时间组均出现了统计学上显著的功能改善（急性组，平均9.2±4.5，P = 0.016；亚急性组，平均11.1±6.8，P = 0.042；慢性组，平均11.3±5.8，P = 0.035）。尽管接受hNSCs的组之间最终BBB评分没有显著差异，但从细胞注射时起改善最大的组是亚急性组（+10.3），且显著大于慢性组（+5.1，P = 0.02）。
结论
在大鼠脊髓挫伤后，将hNSCs经鞘内远端移植到脊髓中，在脊髓损伤（SCI）的急性、亚急性和慢性阶段注射时均导致脊髓功能显著恢复，尽管最大的改善似乎出现在亚急性时间组。
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