一种促进神经干细胞/祖细胞迁移和神经元分化以修复脊髓损伤的功能性支架。

A functional scaffold to promote the migration and neuronal differentiation of neural stem/progenitor cells for spinal cord injury repair.

作者信息

Liu Weiyuan, Xu Bai, Xue Weiwei, Yang Bin, Fan Yongheng, Chen Bing, Xiao Zhifeng, Xue Xiaoyu, Sun Zheng, Shu Muya, Zhang Qi, Shi Ya, Zhao Yannan, Dai Jianwu

机构信息

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100190, China.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100190, China.

出版信息

Biomaterials. 2020 Jun;243:119941. doi: 10.1016/j.biomaterials.2020.119941. Epub 2020 Mar 5.

Abstract

After spinal cord injury (SCI), endogenous neural/progenitor stem cells (NSPCs) were activated in neural tissue adjacent to the injured segment, but few cells migrated to the injury epicenter and differentiated into neurons. N-cadherin regulates mechanical adhesion between NSPCs, and also drives NSPCs migration and promotes NSPCs differentiation. In this study, linearly ordered collagen scaffold (LOCS) was modified with N-cadherin through a two-step cross-linking between thiol and amino group. The results indicated that N-cadherin modification improved the adhesion of NSPCs on collagen scaffold and increased the differentiation into neurons. When LOCS-Ncad was transplanted into complete transected rat spinal cords, more NSPCs migrated to the lesion center and more newborn neurons appeared within the injury site. Furthermore, rats transplanted with LOCS-Ncad showed significantly improved locomotor recovery compared with the rats without implants. Collectively, our results suggest that LOCS-Ncad may be a promising treatment option to facilitate SCI repair by recruiting endogenous NSPCs to the lesion center and promoting neuronal differentiation.

摘要

脊髓损伤(SCI)后,内源性神经/祖干细胞(NSPCs)在损伤节段相邻的神经组织中被激活,但很少有细胞迁移到损伤中心并分化为神经元。N-钙黏蛋白调节NSPCs之间的机械黏附,还驱动NSPCs迁移并促进NSPCs分化。在本研究中,通过硫醇和氨基之间的两步交联,用N-钙黏蛋白修饰线性有序胶原支架(LOCS)。结果表明,N-钙黏蛋白修饰改善了NSPCs在胶原支架上的黏附,并增加了其向神经元的分化。当将LOCS-Ncad移植到完全横断的大鼠脊髓中时,更多的NSPCs迁移到损伤中心,损伤部位出现了更多新生神经元。此外,与未植入的大鼠相比,移植了LOCS-Ncad的大鼠运动功能恢复明显改善。总的来说,我们的结果表明,LOCS-Ncad可能是一种有前景的治疗选择,通过将内源性NSPCs募集到损伤中心并促进神经元分化来促进SCI修复。

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