长效缓释H2S磁流体水凝胶复合iNESC修复脊髓损伤的作用及机制

脊髓损伤（SCI）后，早期级联炎症反应造成神经组织坏死和空洞持续扩大以及晚期轴突不能有效通过瘢痕界面已成为制约SCI治疗的关键问题。我们发表文章已证实，重编程的神经干细胞复合神经支架可有效修复SCI。本课题组前期研究发现，硫化氢（H2S）在SCI中具有抗炎、抗纤维化等作用，可有效减轻炎症反应及瘢痕形成。并已制备Fe3S4磁流体水凝胶，证实其可长效缓释H2S。本项目拟用壳聚糖负载Fe3S4磁流体制备水凝胶，同时利用直接重编程的神经上皮干细胞（iNESC）具有更强干性以及增殖、分化能力，将其复合培养修复SCI，检测其能否有效抑制急性炎症反应，改善局部微环境，晚期促进轴突再生通过瘢痕界面，形成功能性神经连接，达到修复脊髓目的。并建立SCI炎症、瘢痕体外模型，应用转录组学、蛋白质组学等技术，筛查抗炎、抗瘢痕作用的相关靶基因/靶通路，探讨Fe3S4磁流体水凝胶的作用机制，为其进一步应用提供理论依据。

After the occurrence of spinal cord injury (SCI), the necrosis of nerve tissue and the continuous enlargement of cavity caused by cascade inflammation in the early stage and the inability of axons to effectively pass through the glial scar in the late stage have become the key problems restricting the recovery from SCI. Our published articles have confirmed that reprogrammed neural stem cells in combination with neural scaffolds can effectively promote recovery from SCI. We previously found that hydrogen sulfide (H2S) has anti-inflammatory and anti-fibrosis effects in SCI, which can effectively alleviate inflammation and glia scar formation. Fe3S4 ferrofluid hydrogel has been prepared to release H2S continuous. We intends to combine chitosan-Fe3S4 ferrofluid hydrogel with induced neuroepithelial stem cell (iNESC) which has better stemness, to evaluate their effects in inhibiting acute inflammation, improving local microenvironment, and promoting axon regeneration across the glial scar to form functional connection. Besides, we will further explore the mechanism of Fe3S4 ferrofluid hydrogel in established the models of SCI inflammation and glial scar formation in vitro, and apply the transcriptome and proteomics techniques to screen the target genes and target pathways related to anti-inflammatory and anti-scar effects. This study will explore the mechanism of Fe3S4 ferrofluid hydrogel in repairing SCI and thus, provide scientific evidences for its further application in clinic.