Alignment of Astrocytes Increases Neuronal Growth in Three-Dimensional Collagen Gels and Is Maintained Following Plastic Compression to Form a Spinal Cord Repair Conduit

Alignment of Astrocytes Increases Neuronal Growth in Three-Dimensional Collagen Gels and Is Maintained Following Plastic Compression to Form a Spinal Cord Repair Conduit
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DOI:
10.1089/ten.tea.2010.0017
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发表时间:
2010-10-01
影响因子:
4.1
通讯作者:
Phillips, James B.
Phillips, James B.
中科院分区:
医学3区
文献类型:
--
作者:
East, Emma;de Oliveira, Daniela Blum;Phillips, James B.

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脊髓损伤后,反应性星形胶质细胞形成由高度分支的细胞突起组成的神经胶质疤痕,构成修复的主要障碍,部分原因是它们缺乏再生轴突的方向和指导。在一些非哺乳动物脊椎动物中,中枢神经系统的成功再生归因于反应性神经胶质细胞的排列,它引导轴突穿过病变部位。在这里,使用三维哺乳动物细胞接种的胶原凝胶培养系统来探索星形胶质细胞排列对神经元生长的影响。星形胶质细胞的排列被绘制在系留的矩形凝胶内,并且与对照未排列区域相比,在凝胶的边缘和中部显着更大。当神经元接种在星形胶质细胞凝胶上和星形胶质细胞凝胶内时,星形胶质细胞排列区域的神经突长度最大。对齐区域和对照区域之间星形胶质细胞反应性标记物的表达没有差异。在确定了星形胶质细胞排列的潜在效用后,排列好的凝胶被塑料压缩,将它们转变为机械坚固的可植入装置。压缩后,星形胶质细胞保持活力、排列并支持神经突生长,产生了一种组装适合组织工程的排列细胞结构的新方法,并强调了星形胶质细胞排列作为脊髓修复未来可能的治疗干预的重要性。
After injury to the spinal cord, reactive astrocytes form a glial scar consisting of highly ramified cell processes that constitute a major impediment to repair, partly due to their lack of orientation and guidance for regenerating axons. In some nonmammalian vertebrates, successful central nervous system regeneration is attributed to the alignment of reactive glia, which guide axons across the lesion site. Here, a three-dimensional mammalian cell-seeded collagen gel culture system was used to explore the effect of astrocyte alignment on neuronal growth. Astrocyte alignment was mapped within tethered rectangular gels and was significantly greater at the edge and middle of the gels compared to the control unaligned regions. When neurons were seeded on and within astrocyte gels, neurite length was greatest in the areas of astrocyte alignment. There was no difference in expression of astrocyte reactivity markers between aligned and control areas. Having established the potential utility of astrocyte alignment, the aligned gels were plastic compressed, transforming them into mechanically robust implantable devices. After compression, astrocytes remained viable and aligned and supported neurite outgrowth, yielding a novel method for assembling aligned cellular constructs suitable for tissue engineering and highlighting the importance of astrocyte alignment as a possible future therapeutic intervention for spinal cord repair.