Department of Neurobiology, Beijing Institute for Brain Disorders, Beijing Center of Neural Regeneration and Repair, Beijing Key Laboratory of Major Brain Disorders, Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, China.
School of Materials Science and Engineering, University of Science and Technology Beijing, 30 Xueyuan Road, Beijing 100083, China.
Sci Rep. 2016 Sep 19;6:33428. doi: 10.1038/srep33428.
This study examined sustained co-delivery of vascular endothelial growth factor (VEGF), angiopoietin-1 and basic fibroblast growth factor (bFGF) encapsulated in angiogenic microspheres. These spheres were delivered to sites of spinal cord contusion injury in rats, and their ability to induce vessel formation, neural regeneration and improve hindlimb motor function was assessed. At 2-8 weeks after spinal cord injury, ELISA-determined levels of VEGF, angiopoietin-1, and bFGF were significantly higher in spinal cord tissues in rats that received angiogenic microspheres than in those that received empty microspheres. Sites of injury in animals that received angiogenic microspheres also contained greater numbers of isolectin B4-binding vessels and cells positive for nestin or β III-tubulin (P < 0.01), significantly more NF-positive and serotonergic fibers, and more MBP-positive mature oligodendrocytes. Animals receiving angiogenic microspheres also suffered significantly less loss of white matter volume. At 10 weeks after injury, open field tests showed that animals that received angiogenic microspheres scored significantly higher on the Basso-Beattie-Bresnahan scale than control animals (P < 0.01). Our results suggest that biodegradable, biocompatible PLGA microspheres can release angiogenic factors in a sustained fashion into sites of spinal cord injury and markedly stimulate angiogenesis and neurogenesis, accelerating recovery of neurologic function.
本研究考察了血管内皮生长因子（VEGF）、血管生成素-1 和碱性成纤维细胞生长因子（bFGF）在血管生成微球中持续共递的情况。这些球体被递送到大鼠脊髓挫伤损伤部位，评估它们诱导血管形成、神经再生和改善后肢运动功能的能力。在脊髓损伤后 2-8 周，ELISA 测定的血管生成微球组大鼠脊髓组织中 VEGF、血管生成素-1 和 bFGF 的水平明显高于空微球组。接受血管生成微球的动物损伤部位还含有更多的异硫氰酸荧光素 B4 结合血管和巢蛋白或 β III-微管蛋白阳性细胞（P<0.01），NF 阳性和 5-羟色胺能纤维以及更多 MBP 阳性成熟少突胶质细胞。接受血管生成微球的动物白质体积的损失也明显较少。在损伤后 10 周，旷场测试显示，接受血管生成微球的动物在 Basso-Beattie-Bresnahan 量表上的得分明显高于对照组动物（P<0.01）。我们的结果表明，可生物降解、生物相容的 PLGA 微球可以持续将血管生成因子释放到脊髓损伤部位，并显著刺激血管生成和神经发生，加速神经功能的恢复。
