Group of Vascular Regeneration Research, Institute of Biomedical Research and Innovation, Kobe, Hyogo, Japan.
J Neurosci Res. 2012 Dec;90(12):2281-92. doi: 10.1002/jnr.23113. Epub 2012 Sep 20.
Spinal cord injury causes initial mechanical damage, followed by ischemia-induced, secondary degeneration, worsening the tissue damage. Although endothelial progenitor cells (EPCs) have been reported to play an important role for pathophysiological neovascularization in various ischemic tissues, the EPC kinetics following spinal cord injury have never been elucidated. In this study, we therefore assessed the in vivo kinetics of bone marrow-derived EPCs by EPC colony-forming assay and bone marrow transplantation from Tie2/lacZ transgenic mice into wild-type mice with spinal cord injury. The number of circulating mononuclear cells and EPC colonies formed by the mononuclear cells peaked at day 3 postspinal cord injury. Bone marrow transplantation study revealed that bone marrow-derived EPCs recruited into the injured spinal cord markedly increased at day 7, when neovascularization and astrogliosis drastically occurred in parallel with axon growth in the damaged tissue. To elucidate further the contribution of EPCs to recovery after spinal cord injury, exogenous EPCs were systemically infused immediately after the injury. The administered EPCs were incorporated into the injured spinal cord and accelerated neovascularization and astrogliosis. These findings suggest that bone marrow-derived EPCs may contribute to the tissue repair by augmenting neovascularization and astrogliosis following spinal cord injury.
脊髓损伤导致初始的机械损伤，随后是缺血诱导的继发性变性，使组织损伤恶化。尽管内皮祖细胞（EPCs）已被报道在各种缺血组织的病理血管生成中发挥重要作用，但脊髓损伤后 EPC 的动力学尚未阐明。在这项研究中，我们通过 EPC 集落形成测定和 Tie2/lacZ 转基因小鼠的骨髓移植到脊髓损伤的野生型小鼠中，评估了骨髓源性 EPC 的体内动力学。循环单核细胞的数量和单核细胞形成的 EPC 集落在脊髓损伤后第 3 天达到峰值。骨髓移植研究表明，骨髓源性 EPCs 在第 7 天明显募集到损伤的脊髓中，此时血管生成和星形胶质细胞增生与损伤组织中的轴突生长平行发生。为了进一步阐明 EPCs 对脊髓损伤后恢复的贡献，我们在损伤后立即系统输注外源性 EPCs。给予的 EPCs 被整合到损伤的脊髓中，并加速了血管生成和星形胶质细胞增生。这些发现表明，骨髓源性 EPCs 可能通过增强脊髓损伤后的血管生成和星形胶质细胞增生来促进组织修复。
