Olfactory ensheathing cells promote neurite sprouting of injured axons in vitro by direct cellular contact and secretion of soluble factors
Olfactory ensheathing cells promote neurite sprouting of injured axons in vitro by direct cellular contact and secretion of soluble factors
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DOI：
10.1007/s00018-004-4026-y
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发表时间：
2004-05-01
影响因子：
8
通讯作者：
Chuah, MI
中科院分区：
文献类型：
--
作者：
Chung, RS;Woodhouse, A;Chuah, MI
嗅鞘细胞（OECs）代表了一个令人兴奋的可能性，促进损伤的脊髓轴突再生。许多研究表明，这些细胞能够促进受损脊髓内受损轴突的显着反应性发芽，并在某些情况下恢复功能能力。然而，OEC用于实现这一目标的细胞和/或分子机制尚不清楚。为了研究这种机制，我们首次报道了嗅鞘细胞在体外轴突损伤模型中促进损伤后神经突发芽的能力。使用这个模型，我们能够区分直接和间接的机制，OECs的能力，以促进神经元从损伤中恢复。我们注意到，嗅鞘细胞似乎作为一个物理基板的生长损伤后的神经突芽。我们还发现，虽然当OECs被允许直接接触受伤的神经元时，损伤后发芽得到了最大程度的促进，但使用组织培养插入物（1 mm孔径，可渗透扩散因子但不可渗透细胞）的物理分离并没有完全阻断OECs的促进特性，这表明它们还分泌可溶性因子，这有助于损伤后神经突发芽。此外，该体外模型允许使用活细胞成像技术直接观察OEC和出芽神经突之间的细胞相互作用。总之，我们发现嗅鞘细胞分别通过提供生长的物理基质和通过可溶性因子的表达来促进神经突发芽。我们的研究结果为OECs促进轴突再生的能力提供了新的见解，也为操纵这些细胞以增强其恢复能力提供了潜在的靶点。
Olfactory ensheathing cells (OECs) represent an exciting possibility for promoting axonal regeneration within the injured spinal cord. A number of studies have indicated the ability of these cells to promote significant reactive sprouting of injured axons within the injured spinal cord, and in some cases restoration of functional abilities. However, the cellular and/or molecular mechanisms OECs use to achieve this are unclear. To investigate such mechanisms, we report for the first time the ability of OECs to promote post-injury neurite sprouting in an in vitro model of axonal injury. Using this model, we were able to differentiate between the direct and indirect mechanisms underlying the ability of OECs to promote neuronal recovery from injury. We noted that OECs appeared to act as a physical substrate for the growth of post-injury neurite sprouts. We also found that while post-injury sprouting was promoted most when OECs were allowed to directly contact injured neurons, physical separation using tissue culture inserts (1 mm pore size, permeable to diffusible factors but not cells) did not completely block the promoting properties of OECs, suggesting that they also secrete soluble factors which aid post-injury neurite sprouting. Furthermore, this in vitro model allowed direct observation of the cellular interactions between OECs and sprouting neurites using live-cell-imaging techniques. In summary, we found that OECs separately promote neurite sprouting by providing a physical substrate for growth and through the expression of soluble factors. Our findings provide new insight into the ability of OECs to promote axonal regeneration, and also indicate potential targets for manipulation of these cells to enhance their restorative ability.