Schwann Cell Coculture Improves the Therapeutic Effect of Bone Marrow Stromal Cells on Recovery in Spinal Cord-Injured Mice
Schwann Cell Coculture Improves the Therapeutic Effect of Bone Marrow Stromal Cells on Recovery in Spinal Cord-Injured Mice
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DOI：
10.3727/096368910x544906
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发表时间：
2011-08
影响因子：
3.3
通讯作者：
Xiaoyun Xu;N. Geremia;F. Bao;A. Pniak;M. Rossoni;Arthur Brown
中科院分区：
文献类型：
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作者：
Xiaoyun Xu;N. Geremia;F. Bao;A. Pniak;M. Rossoni;Arthur Brown
对骨髓基质细胞(MSCs)移植到脊髓损伤大鼠的研究给出了不同的结果：一些组报告改善了运动恢复，而另一些组仅证明了损伤的组织学外观改善。这些研究表明，神经功能改善和MSC存活率之间没有明显的相关性。我们研究了通过在遗传背景和标记基因表达方面使供体和受体小鼠紧密匹配，是否可以提高损伤脊髓中MSC的存活率，以及移植前将MSCs暴露在神经环境(雪旺细胞)中是否会改善它们的存活率或治疗效果。小鼠在第四胸椎水平接受脊髓夹压损伤，7天后进行细胞移植。尽管供者和受者的基因匹配，MSC在损伤脊髓中的存活率很低(~1%)。然而，我们注意到，在接受MSC移植的小鼠中，运动恢复的改善伴随着损害的组织病理学外观的改善。这些小鼠有更多的白质和灰质保留，层粘连蛋白表达，雪旺细胞渗透，并保留了病变周围和下方的神经丝和5-羟色胺阳性纤维。在接受MSC移植的小鼠中，瘢痕中胶原和硫酸软骨素蛋白多糖的沉积也减少，巨噬细胞被激活。雪旺细胞共培养的MSCs对上述各项指标的恢复效果均优于未经处理的MSCs。趋化因子和细胞因子表达的分析表明，MSC/Schwann细胞共培养产生的MCP-1和IL-6远低于MSCs或Schwann细胞单独培养。因此，移植的MSCs可能通过雪旺细胞共培养步骤增强的免疫抑制效应来促进脊髓损伤小鼠的恢复。这些结果表明，骨髓间充质干细胞在损伤脊髓中的暂时存在足以改变脊髓损伤后通常发生的一系列病理事件，产生有利于改善恢复的微环境。
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.