The Spinal Cord Injury Team, BioTherapeutics Research Laboratories and Molecular Brain Research Group, Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada.
Cell Transplant. 2011;20(7):1065-86. doi: 10.3727/096368910X544906. Epub 2010 Nov 19.
Studies of bone marrow stromal cells (MSCs) transplanted into the spinal cord-injured rat give mixed results: some groups report improved locomotor recovery while others only demonstrate improved histological appearance of the lesion. These studies show no clear correlation between neurological improvements and MSC survival. We examined whether MSC survival in the injured spinal cord could be enhanced by closely matching donor and recipient mice for genetic background and marker gene expression and whether exposure of MSCs to a neural environment (Schwann cells) prior to transplantation would improve their survival or therapeutic effects. Mice underwent a clip compression spinal cord injury at the fourth thoracic level and cell transplantation 7 days later. Despite genetic matching of donors and recipients, MSC survival in the injured spinal cord was very poor (∼1%). However, we noted improved locomotor recovery accompanied by improved histopathological appearance of the lesion in mice receiving MSC grafts. These mice had more white and gray matter sparing, laminin expression, Schwann cell infiltration, and preservation of neurofilament and 5-HT-positive fibers at and below the lesion. There was also decreased collagen and chondroitin sulphate proteoglycan deposition in the scar and macrophage activation in mice that received the MSC grafts. The Schwann cell cocultured MSCs had greater effects than untreated MSCs on all these indices of recovery. Analyses of chemokine and cytokine expression revealed that MSC/Schwann cell cocultures produced far less MCP-1 and IL-6 than MSCs or Schwann cells cultured alone. Thus, transplanted MSCs may improve recovery in spinal cord-injured mice through immunosuppressive effects that can be enhanced by a Schwann cell coculturing step. These results indicate that the temporary presence of MSCs in the injured cord is sufficient to alter the cascade of pathological events that normally occurs after spinal cord injury, generating a microenvironment that favors improved recovery.
骨髓基质细胞（MSCs）移植入脊髓损伤大鼠的研究结果喜忧参半：一些研究小组报告运动功能恢复改善，而另一些仅显示病变的组织学外观改善。这些研究表明，神经功能改善与 MSC 存活之间没有明显的相关性。我们研究了通过密切匹配供体和受体小鼠的遗传背景和标记基因表达，是否可以增强 MSC 在损伤脊髓中的存活，以及在移植前将 MSC 暴露于神经环境（施万细胞）是否会提高其存活或治疗效果。小鼠在第四胸椎水平进行夹压脊髓损伤，7 天后进行细胞移植。尽管供体和受体的遗传匹配，但 MSC 在损伤脊髓中的存活非常差（约 1%）。然而，我们注意到接受 MSC 移植物的小鼠运动功能恢复改善，病变的组织学外观也得到改善。这些小鼠在损伤处和损伤以下部位具有更多的白质和灰质保留、层粘连蛋白表达、施万细胞浸润以及神经丝和 5-HT 阳性纤维的保留。接受 MSC 移植物的小鼠在疤痕中的胶原和软骨素硫酸蛋白聚糖沉积以及巨噬细胞激活也减少。与未处理的 MSC 相比，施万细胞共培养的 MSC 对所有这些恢复指标都有更大的影响。趋化因子和细胞因子表达分析表明，MSC/施万细胞共培养产生的 MCP-1 和 IL-6 远少于单独培养的 MSC 或施万细胞。因此，移植的 MSC 可能通过免疫抑制作用改善脊髓损伤小鼠的恢复，这种作用可以通过施万细胞共培养步骤得到增强。这些结果表明，MSC 在损伤脊髓中的短暂存在足以改变正常发生在脊髓损伤后的病理事件级联，产生有利于改善恢复的微环境。
