Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury
Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury
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DOI：
10.1523/jneurosci.0143-08.2008
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发表时间：
2008-04-02
影响因子：
5.3
通讯作者：
Kessler, John A.
中科院分区：
文献类型：
--
作者：
Tysseling-Mattiace, Vicki M.;Sahni, Vibhu;Kessler, John A.
在体内自组装成超分子纳米纤维的肽两亲物（PA）分子被用作脊髓损伤（SCI）小鼠模型的治疗。由于这些分子的自组装是由体内环境的离子强度触发的，因此可以通过简单地注射液体在脊髓的细胞外空间内产生纳米级结构。这些分子被设计成形成圆柱形纳米纤维，其以接近货车德瓦耳斯密度向脊髓中的细胞展示层粘连蛋白表位IKVAV。已知IKVAV PA纳米纤维抑制培养的神经干细胞的神经胶质分化并促进培养的神经元的神经突生长。在这项工作中，在SCI后用PA进行体内治疗减少了星形胶质细胞增生，减少了细胞死亡，并增加了损伤部位少突胶质细胞的数量。此外，纳米纤维促进了损伤部位下行运动纤维和上行感觉纤维的再生。PA治疗也导致了显着的行为改善。这些观察结果表明，使用表面显示高密度神经活性表位的生物活性三维纳米结构可以抑制胶质疤痕形成并促进SCI后的再生。
Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury ( SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces.