Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
Department of Orthopaedics, The General Hospital of Central Theater Command of People's Liberation Army, Wuhan, People's Republic of China.
Int J Nanomedicine. 2020 Jan 20;15:315-332. doi: 10.2147/IJN.S227328. eCollection 2020.
The clinical outcome of spinal cord injury is usually poor due to the lack of axonal regeneration and glia scar formation. As one of the most classical supporting cells in neural regeneration, Schwann cells (SCs) provide bioactive substrates for axonal migration and release molecules that regulate axonal growth. However, the effect of SC transplantation is limited by their poor migration capacity in the astrocyte-rich central nervous system.
In this study, we first magnetofected SCs with chondroitinase ABC-polyethylenimine functionalized superparamagnetic iron oxide nanoparticles (ChABC/PEI-SPIONs) to induce overexpression of ChABC for the removal of chondroitin sulfate proteoglycans. These are inhibitory factors and forming a dense scar that acts as a barrier to the regenerating axons. In vitro, we observed the migration of SCs in the region of astrocytes after the application of a stable external magnetic field.
We found that magnetofection with ChABC/PEI-SPIONs significantly up-regulated the expression of ChABC in SCs. Under the driven effect of the directional magnetic field (MF), the migration of magnetofected SCs was enhanced in the direction of the magnetic force. The number of SCs with ChABC/PEI-SPIONs migrated and the distance of migration into the astrocyte region was significantly increased. The number of SCs with ChABC/PEI-SPIONs that migrated into the astrocyte region was 11.6- and 4.6-fold higher than those observed for the intact control and non-MF groups, respectively. Furthermore, it was found that SCs with ChABC/PEI-SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF.
The mobility of the SCs with ChABC/PEI-SPIONs was enhanced along the axis of MF, holding the potential to promote nerve regeneration by providing a bioactive microenvironment and relieving glial obstruction to axonal regeneration in the treatment of spinal cord injury.
由于轴突再生和胶质瘢痕形成，脊髓损伤的临床结果通常较差。施万细胞（SCs）作为神经再生中最经典的支持细胞之一，为轴突迁移提供生物活性基质，并释放调节轴突生长的分子。然而，SCs 移植的效果受到其在富含星形胶质细胞的中枢神经系统中迁移能力差的限制。
在这项研究中，我们首先用软骨素酶 ABC-聚乙烯亚胺功能化超顺磁性氧化铁纳米粒子（ChABC/PEI-SPIONs）磁转染 SCs，以诱导 ChABC 的过表达，从而去除硫酸软骨素蛋白聚糖。这些是抑制性因子，形成致密的瘢痕，成为再生轴突的障碍。在体外，我们观察了在施加稳定外磁场后 SCs 在星形胶质细胞区域的迁移。
我们发现 ChABC/PEI-SPIONs 的磁转染显著上调了 SCs 中 ChABC 的表达。在外磁场（MF）的驱动作用下，磁转染的 SCs 的迁移方向增强。具有 ChABC/PEI-SPIONs 的 SCs 的迁移数量和迁移到星形胶质细胞区域的距离明显增加。具有 ChABC/PEI-SPIONs 的 SCs 迁移到星形胶质细胞区域的数量分别比完整对照组和无 MF 组高 11.6 倍和 4.6 倍。此外，还发现具有 ChABC/PEI-SPIONs 的 SCs 在 MF 的存在下与星形胶质细胞紧密接触，不再形成边界。
ChABC/PEI-SPIONs 的 SCs 沿着 MF 的轴迁移的能力增强，通过提供生物活性微环境并缓解胶质对脊髓损伤后轴突再生的阻碍，有可能促进神经再生。
