Group of Vascular Regeneration, Institute of Biomedical Research and Innovation, Hyogo, Japan.
J Neurotrauma. 2012 Jun 10;29(9):1758-69. doi: 10.1089/neu.2011.2139. Epub 2012 May 21.
Interactions between endothelial and neural stem cells are believed to play a critical role in the kinetics of neural stem cells in the central nervous system. Here we demonstrate that endothelial progenitor cells promote the repair of injured spinal cord through the induction of Notch-dependent astrogliosis and vascular regulation. The transplantation of Jagged1(+/+) endothelial progenitor cells, but not Jagged1(-/-) endothelial progenitor cells, increased the number of reactive astrocytes during the acute phase, and improved functional recovery following spinal cord injury. Expression of the Notch effector Hes5 was upregulated in the injured spinal cord after Jagged1(+/+) endothelial progenitor cell transplantation. Furthermore, we found that the Notch ligand Delta-like-1 was highly expressed in Jagged1(-/-) endothelial progenitor cells. Transplantation of Delta-like-1, as well as Jagged1-overexpressing 3T3 cells, revealed that only Jagged1-overexpressing 3T3 stromal cells enhanced astrogliosis following spinal cord injury. In addition, Jagged1(+/+) endothelial progenitor cells exhibited not only dramatic pro-angiogenic effects, but also morphologically abnormal vessel stabilization, compared with Jagged1(-/-)endothelial progenitor cells in injured spinal cord. Thus, transplanted endothelial progenitor cells promote astrogliosis, vascular regulation, and spinal cord regeneration through activation of Jagged1-Notch signaling.
内皮祖细胞和神经干细胞之间的相互作用被认为在中枢神经系统中神经干细胞的动力学中起着关键作用。在这里，我们证明内皮祖细胞通过诱导 Notch 依赖性星形胶质细胞增生和血管调节来促进损伤脊髓的修复。Jagged1(+/+)内皮祖细胞的移植而非 Jagged1(-/-)内皮祖细胞的移植增加了急性阶段反应性星形胶质细胞的数量，并改善了脊髓损伤后的功能恢复。Jagged1(+/+)内皮祖细胞移植后，损伤脊髓中 Notch 效应物 Hes5 的表达上调。此外，我们发现 Notch 配体 Delta-like-1 在 Jagged1(-/-)内皮祖细胞中高度表达。Delta-like-1 以及 Jagged1 过表达的 3T3 细胞的移植表明，只有 Jagged1 过表达的 3T3 基质细胞增强了脊髓损伤后的星形胶质细胞增生。此外，与损伤脊髓中的 Jagged1(-/-)内皮祖细胞相比，移植的内皮祖细胞不仅表现出显著的促血管生成作用，而且还表现出形态异常的血管稳定作用。因此，移植的内皮祖细胞通过激活 Jagged1-Notch 信号通路促进星形胶质细胞增生、血管调节和脊髓再生。
