Therapeutic benefit of intrathecal injection of marrow stromal cells on ischemia-injured spinal cord
Therapeutic benefit of intrathecal injection of marrow stromal cells on ischemia-injured spinal cord
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DOI：
10.1016/j.athoracsur.2006.11.048
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发表时间：
2007-04-01
影响因子：
4.6
通讯作者：
Bashar, Abul Hasan Muhammad
中科院分区：
文献类型：
--
作者：
Shi, Enyi;Kazui, Teruhisa;Bashar, Abul Hasan Muhammad
背景在脊髓缺血前预防性移植骨髓基质细胞（MSCs）已被证明可以减轻神经损伤。我们试图研究骨髓间充质干细胞对缺血损伤脊髓的治疗作用。骨髓基质细胞体外扩增，溴脱氧尿苷预标记。通过肾下主动脉阻断30分钟诱导兔脊髓缺血。共入组4组。分别于脊髓缺血后2h（MSC-2h组）、24h（MSC-24h组）和48h（MSC-48h组）鞘内注射约1 × 108个MSC。对照组仅鞘内注射培养基。在28天的恢复期内，采用Tarlov标准评估后肢运动功能，然后进行组织学检查。移植后4周，脊髓内仍可见骨髓基质细胞。在三个MSC处理组中，腹侧灰质中的毛细血管密度显著增加（分别与对照组相比p <0.01）。在28天恢复后，在MSC-2h组（从第1天到第28天，分别与对照组相比，p <0.05）和MSC-24h组（从第14天到第28天，分别与对照组相比，p <0.05）中检测到显著的功能改善，但在MSC-48h组中没有。MSC-2h组完整运动神经元数量明显多于对照组（p <0.05）。鞘内注射骨髓间充质干细胞促进宿主脊髓血管新生，促进脊髓缺血后运动功能恢复。治疗时间窗对于MSC的治疗效果至关重要。
Background. Prophylactic transplantation of marrow stromal cells (MSCs) before spinal cord ischemia has been shown to attenuate neurologic injures. We sought to investigate the therapeutic effect of MSCs on ischemia-injured spinal cord.Methods. Marrow stromal cells were expanded in vitro and prelabeled with bromodeoxyuridine. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Four groups were enrolled. About 1 x 108 MSCs were intrathecally injected 2 hours (group MSC-2h), 24 hours (group MSC-24h), or 48 hours (group MSC-48h) after spinal cord ischemia, respectively. The control group received intrathecal injection of medium alone. Hind-limb motor function was assessed during a 28-day recovery period with Tarlov criteria, and then histologic examination was performed.Results. Marrow stromal cells still could be found in the spinal cord 4 weeks after transplantation. The capillary density in the ventral gray matter was significantly increased in the three MSC-treated groups (p < 0.01 versus control group, respectively). After a 28-day recovery, marked functional improvement was detected in group MSC-2h (from day 1 to 28, p < 0.05, versus control group, respectively) and group MSC-24h (from day 14 to 28, p < 0.05, versus control group, respectively), but not in group MSC-48h. The number of intact motor neurons was much greater in group MSC-2h (p < 0.05, versus control group).Conclusions. Intrathecal injection of MSCs enhances angiogenesis in the host spinal cord and improves the motor functional recovery after spinal cord ischemia. The therapeutic time window is critical for the therapeutic effect of MSCs.