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三维纳米纤维支架结合固定化脑源性神经营养因子促进皮质神经干细胞的增殖和分化。

Three-dimensional nanofibrous scaffolds incorporating immobilized BDNF promote proliferation and differentiation of cortical neural stem cells.

机构信息

Florey Neuroscience Institutes and Centre for Neurosciences, University of Melbourne, Melbourne, Australia.

出版信息

Stem Cells Dev. 2010 Jun;19(6):843-52. doi: 10.1089/scd.2009.0158.

Abstract

Attempts to repair the central nervous system damaged as a result of trauma or disease will depend on the ability to restore the appropriate neuronal connectivity. This will rely on establishing appropriate chemical and physical environments for supporting neural cells and their processes and in this regard, engineering of biomaterials is of increasing interest. It will be important to understand how cells behave on these biomaterials in vitro, prior to future in vivo application. We reveal that modification of 3-dimensional (3D) electrospun poly-epsilon-caprolactone (PCL) nanofiber scaffolds by fiber alignment and aminolysation is superior to classical 2-dimensional (2D) culture-ware in promoting in vitro proliferation and differentiation of cortical cells. Many studies have examined the importance of exogenous soluble factors to promote cell fate specification. Here, we demonstrate that tethering the neurotrophin, brain-derived neurotrophic factor (BDNF), onto modified nanofibers is superior to culturing in the presence of soluble BDNF. Functional immobilization of BDNF to polymer nanofibers enhances neural stem cell (NSC) proliferation and directs cell fate toward neuronal and oligodendrocyte specification, essential for neural tissue repair. These findings indicate that modified PCL nanofibrous 3D scaffolds are capable of supporting NSCs and their derivatives and may present a new avenue for encouraging neural repair in the future.

摘要

试图修复因创伤或疾病而受损的中枢神经系统将取决于恢复适当神经元连接的能力。这将依赖于为支持神经细胞及其过程建立适当的化学和物理环境,在这方面,生物材料的工程学越来越受到关注。在未来的体内应用之前,了解细胞在这些生物材料上的体外行为将是很重要的。我们揭示了通过纤维取向和氨化修饰三维(3D)静电纺聚己内酯(PCL)纳米纤维支架,优于经典的二维(2D)培养皿,可促进皮质细胞的体外增殖和分化。许多研究已经研究了外源性可溶性因子在促进细胞命运特化中的重要性。在这里,我们证明将神经营养因子脑源性神经营养因子(BDNF)固定在改性纳米纤维上优于在存在可溶性 BDNF 的情况下进行培养。BDNF 到聚合物纳米纤维的功能固定可增强神经干细胞(NSC)的增殖,并将细胞命运引导到神经元和少突胶质细胞特化,这对于神经组织修复至关重要。这些发现表明,改性的 PCL 纳米纤维 3D 支架能够支持 NSCs 及其衍生物,并且可能为未来促进神经修复提供新途径。

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