Department of Clinical and Biological Sciences (DSCB), University of Torino, 10043 Orbassano (Torino), Italy.
Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, 10043 Orbassano (Torino), Italy.
Cells. 2020 Jun 1;9(6):1366. doi: 10.3390/cells9061366.
Conduits for the repair of peripheral nerve gaps are a good alternative to autografts as they provide a protected environment and a physical guide for axonal re-growth. Conduits require colonization by cells involved in nerve regeneration (Schwann cells, fibroblasts, endothelial cells, macrophages) while in the autograft many cells are resident and just need to be activated. Since it is known that soluble Neuregulin1 (sNRG1) is released after injury and plays an important role activating Schwann cell dedifferentiation, its expression level was investigated in early regeneration steps (7, 14, 28 days) inside a 10 mm chitosan conduit used to repair median nerve gaps in Wistar rats. In vivo data show that sNRG1, mainly the isoform α, is highly expressed in the conduit, together with a fibroblast marker, while Schwann cell markers, including NRG1 receptors, were not. Primary culture analysis shows that nerve fibroblasts, unlike Schwann cells, express high NRG1α levels, while both express NRG1β. These data suggest that sNRG1 might be mainly expressed by fibroblasts colonizing nerve conduit before Schwann cells. Immunohistochemistry analysis confirmed NRG1 and fibroblast marker co-localization. These results suggest that fibroblasts, releasing sNRG1, might promote Schwann cell dedifferentiation to a "repair" phenotype, contributing to peripheral nerve regeneration.
用于修复周围神经间隙的导管是自体移植物的良好替代品，因为它们为轴突再生提供了一个受保护的环境和物理引导。导管需要被参与神经再生的细胞（雪旺细胞、成纤维细胞、内皮细胞、巨噬细胞）殖民化，而在自体移植物中，许多细胞是常驻的，只需要被激活。由于已知可溶性神经调节蛋白 1（sNRG1）在损伤后释放，并在激活雪旺细胞去分化中发挥重要作用，因此研究了其在使用 10mm 壳聚糖导管修复 Wistar 大鼠正中神经间隙的早期再生步骤（7、14、28 天）中的表达水平。体内数据表明，sNRG1，主要是同工型α，在导管中高度表达，与成纤维细胞标志物一起表达，而雪旺细胞标志物，包括 NRG1 受体，不表达。原代培养分析表明，神经成纤维细胞与雪旺细胞不同，表达高水平的 NRG1α，而两者均表达 NRG1β。这些数据表明，sNRG1 可能主要由殖民导管的成纤维细胞表达，然后是雪旺细胞。免疫组织化学分析证实了 NRG1 和成纤维细胞标志物的共定位。这些结果表明，释放 sNRG1 的成纤维细胞可能促进雪旺细胞去分化为“修复”表型，有助于周围神经再生。
