Does timing of transplantation of neural stem cells following spinal cord injury affect outcomes in an animal model?
Does timing of transplantation of neural stem cells following spinal cord injury affect outcomes in an animal model?
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DOI：
10.21037/jss.2017.10.06
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发表时间：
2017-12-01
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影响因子：
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通讯作者：
Kharazi, Alexander I
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文献类型：
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作者：
Cheng, Ivan;Park, Don Y;Kharazi, Alexander I
背景技术背景：我们以前报道过，急性移植神经干细胞到损伤部位远端后，脊髓挫伤大鼠的功能恢复可以发生。探讨在动物模型中脊髓损伤部位远端给予人神经干细胞（hNSC）对功能结果的影响。方法：将36只成年雌性Long-Evans hooded大鼠随机分为3个实验组和3个对照组，每组6只。通过后路椎板切除术暴露T10节段，并通过多中心动物脊髓损伤研究撞击器（MASCIS，W.M. Keck神经科学协作中心，皮斯卡特维，NJ，USA）。在诱导的脊髓损伤后立即、一周或四周，通过单独的远端椎板切开术，动物接受hNSCs或对照培养基的鞘内注射。观察员对干预措施不知情。损伤后立即和每周使用Basso，Beattie，Bresnahan（BBB）运动评分进行功能评估。结果：与对照组相比，所有三个时间组的功能改善具有统计学意义（急性，平均9.2 vs. 4.5，P=0.016;亚急性，平均11.1 vs. 6.8，P=0.042;慢性，平均11.3 vs. 5.8，P=0.035）。虽然接受hNSC的组与接受hNSC的组相比，最终BBB评分没有显著差异，但从细胞注射时起实现最大改善的组是亚急性组（+10.3），显著大于慢性组（+5.1，P =0.02）.结论：将hNSCs远端鞘内移植到大鼠挫伤的脊髓中，当注射时，脊髓的功能显著恢复。在脊髓损伤（SCI）的急性、亚急性和慢性阶段，尽管最大的收益似乎是在亚急性时间组。
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 vs. 4.5, P=0.016; subacute, mean 11.1 vs. 6.8, P=0.042; chronic, mean 11.3 vs. 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.