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一种带有 EGFR 抗体的双重功能支架可促进神经干细胞的保留和分化,用于脊髓损伤修复。

A Dual Functional Scaffold Tethered with EGFR Antibody Promotes Neural Stem Cell Retention and Neuronal Differentiation for Spinal Cord Injury Repair.

机构信息

Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, P. R. China.

Center for Regenerative Medicine, State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, P. R. China.

出版信息

Adv Healthc Mater. 2017 May;6(9). doi: 10.1002/adhm.201601279. Epub 2017 Feb 24.

Abstract

Neural stem cells (NSCs) transplantation is a promising strategy to restore neuronal relays and neurological function of injured spinal cord because of the differentiation potential into functional neurons, but the transplanted NSCs often largely diffuse from the transplanted site and mainly differentiate into glial cells rather than neurons due to the adverse microenviornment after spinal cord injury (SCI). This paper fabricates a dual functional collagen scaffold tethered with a collagen-binding epidermal growth factor receptor (EGFR) antibody to simultaneously promote NSCs retention and neuronal differentiation by specifically binding to EGFR molecule expressed on NSCs and attenuating EGFR signaling, which is responsible for the inhibition of differentiation of NSCs toward neurons. Compared to unmodified control scaffold, the dual functional scaffold promotes the adhesion and neuronal differentiation of NSCs in vitro. Moreover, the implantation of the dual functional scaffold with exogenous NSCs in rat SCI model can capture and retain NSCs at the injury sites, and promote the neuronal differentiation of the retained NSCs into functional neurons, and finally dedicate to improving motor function of SCI rats, which provides a potential strategy for synchronously promoting stem cell retention and differentiation with biomaterials for SCI repair.

摘要

神经干细胞(NSCs)移植是一种很有前途的策略,可以恢复损伤脊髓的神经元传递和神经功能,因为其具有分化为功能性神经元的潜力,但由于脊髓损伤(SCI)后的不良微环境,移植的 NSCs 往往会从移植部位大量扩散,并主要分化为胶质细胞而不是神经元。本文构建了一种具有双重功能的胶原支架,该支架通过与 NSCs 上表达的胶原结合型表皮生长因子受体(EGFR)抗体特异性结合,同时促进 NSCs 的保留和神经元分化,从而减弱 EGFR 信号,抑制 NSCs 向神经元分化。与未修饰的对照支架相比,双重功能支架在体外促进了 NSCs 的黏附和神经元分化。此外,在大鼠 SCI 模型中植入具有外源性 NSCs 的双重功能支架可以在损伤部位捕获和保留 NSCs,并促进保留的 NSCs 向功能性神经元分化,最终有助于改善 SCI 大鼠的运动功能,为同步促进干细胞保留和分化提供了一种有潜力的策略,这对于 SCI 修复的生物材料来说是非常重要的。

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