Department of Life Sciences, The Open University, Walton Hall, Milton Keynes, United Kingdom.
Tissue Eng Part A. 2010 Oct;16(10):3173-84. doi: 10.1089/ten.tea.2010.0017.
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.
脊髓损伤后，反应性星形胶质细胞形成胶质瘢痕，由高度分支的细胞突起组成，这是修复的主要障碍，部分原因是它们缺乏对再生轴突的定向和引导。在一些非哺乳动物的脊椎动物中，成功的中枢神经系统再生归因于反应性神经胶质的排列，它引导轴突穿过损伤部位。在这里，使用三维哺乳动物细胞接种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。在束缚的矩形凝胶内绘制星形胶质细胞的排列，并与对照未对齐区域相比，在凝胶的边缘和中间明显更大。当神经元接种在星形胶质细胞凝胶上和内部时，在星形胶质细胞排列区域的神经突长度最大。在对齐和对照区域之间，星形胶质细胞反应性标志物的表达没有差异。在确定了星形胶质细胞排列的潜在用途之后，将对齐的凝胶进行塑性压缩，将其转化为机械坚固的可植入装置。压缩后，星形胶质细胞仍然存活并排列整齐，支持神经突生长，为组装适合组织工程的对齐细胞构建体提供了一种新方法，并强调了星形胶质细胞排列作为脊髓修复未来治疗干预的可能性。
