National Research Centre "Kurchatov Institute", Kurchatov Complex of NBICS-Technologies, Laboratory of Tissue Engineering, Moscow, Russia.
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
Cell Biochem Funct. 2021 Jul;39(5):679-687. doi: 10.1002/cbf.3634. Epub 2021 Apr 26.
The resumption of blood supply in spinal cord (SC) after injury is a prerequisite of its recovery. To expose the mechanisms of damaged SC revascularization we have used an organotypic SC/aortic fragments (AF) co-culture where, as we showed previously, damaged SC tissue induces AF cell sprouting but repels them away. Supplementation of culture medium with exogenous VEGF-A redirects the migrating aortic endothelial cells towards SC tissue. This effect and the pattern of sFlt1 expression (a soluble form of VEGFR1) suggest that the low level of SC-secreted VEGF and the presence of sFlt1 in SC slices together prevent the migration of aortic CD31 cells to the SC in the absence of exogenous VEGF. VEGF-A supplementation sequesters this inhibitory activity of sFlt1 by direct binding thus allowing CD31 cell migration in to SC tissue. Proteome analysis has shown that migration/proliferation of CD31 and αSMA aortic cells in neuronal culture medium used in our SC/AF model (which obstruct sprouting by itself) was resumed by combined action of several pro- (aFGF, bFGF, Osteopontin, TF, IGFBP2, SDF1) and anti-angiogenic (Endostatin/Collagen18) factors. The mutual influence of AF and SC tissues is a key factor balancing these factors and thus driving endothelial sprouting in SC injury zone.
脊髓（SC）损伤后恢复血液供应是其恢复的前提。为了揭示受损 SC 再血管化的机制，我们使用了器官型 SC/主动脉片段（AF）共培养物，如我们之前所示，受损的 SC 组织诱导 AF 细胞发芽，但将其排斥在外。在培养基中补充外源性 VEGF-A 可将迁移的主动脉内皮细胞引导至 SC 组织。这种效应和 sFlt1 表达模式（VEGFR1 的可溶性形式）表明，SC 分泌的 VEGF 水平低，以及 SC 切片中存在 sFlt1，共同防止了在没有外源性 VEGF 的情况下，主动脉 CD31 细胞向 SC 的迁移。VEGF-A 补充剂通过直接结合来隔离这种 sFlt1 的抑制活性，从而允许 CD31 细胞迁移到 SC 组织中。蛋白质组分析表明，在我们的 SC/AF 模型中使用的神经元培养基中（其本身会阻碍发芽），CD31 和 αSMA 主动脉细胞的迁移/增殖，通过几种促（aFGF、bFGF、骨桥蛋白、TF、IGFBP2、SDF1）和抗血管生成（内皮抑素/胶原 18）因子的共同作用得以恢复。AF 和 SC 组织的相互影响是平衡这些因子的关键因素，从而驱动 SC 损伤区的内皮发芽。
