Immobilized concentration gradients of neurotrophic factors guide neurite outgrowth of primary neurons in macroporous scaffolds
Immobilized concentration gradients of neurotrophic factors guide neurite outgrowth of primary neurons in macroporous scaffolds
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DOI：
10.1089/ten.2006.12.267
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发表时间：
2006-02-01
影响因子：
--
通讯作者：
Shoichet, M
中科院分区：
文献类型：
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作者：
Moore, K;Macsween, M;Shoichet, M
以浓度梯度存在的神经营养因子是神经营养性线索，其引导轴突朝向其靶生长。多种因素在体内共同作用，以确保轴突到达适当的目标，可能通过细胞内信号通路相互作用。神经生长因子（NGF）和神经营养因子-3（NT-3）是已知在脊髓和外周神经损伤后引导轴突以及促进轴突生长的神经营养因子。这些分子通过不同的酪氨酸激酶受体与神经元相互作用。在这项研究中，这些生长因子的受体被证明是共同定位于E10鸡背根神经节（DRG）细胞，提供了一个机会，协同作用。明确定义的浓度梯度的神经生长因子和NT-3固定在细胞穿透，细胞粘附支架的聚（2-羟乙基甲基丙烯酸酯）和聚（L-赖氨酸）的第一次。需要310 ng/mL/mm 2的NGF浓度梯度来引导鸡DRG神经突。当还存在200 ng/mL/mm 2的NT-3浓度梯度时，显示200 ng/mL/mm 2的较低浓度梯度的NGF引起引导，表明DRG神经元中的协同反应。这些梯度支架可用于脊髓或外周神经损伤后的引导再生，也可阐明神经营养因子的细胞内信号传导机制。
Neurotrophic factors present as concentration gradients are neurotropic cues that direct axonal growth toward their targets. Multiple factors work together in vivo to ensure axons reach the proper targets, likely interacting with one another via intracellular signalling pathways. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are neurotrophins known to guide axons as well as promote axonal growth following injury to both the spinal cord and peripheral nerve. These molecules interact with neurons through different tyrosine kinase receptors. In this study, the receptors for these growth factors were shown to be co-localized on E10 chick dorsal root ganglion (DRG) cells, providing an opportunity for synergism. Well-defined concentration gradients of NGF and NT-3 were immobilized for the first time in a cell-penetrable, cell-adhesive scaffold of poly(2-hydroxyethylmethacrylate) and poly( L-lysine). An NGF concentration gradient of 310 ng/mL/mm was required to guide chick DRG neurites. A lower concentration gradient of 200 ng/mL/mm of NGF was shown to elicit guidance when an NT-3 concentration gradient of 200 ng/mL/mm was also present, indicating a synergistic response in the DRG neurons. These gradient scaffolds may be useful for guided regeneration following injury to the spinal cord or peripheral nerve and may also elucidate the mechanism for intracellular signaling of neurotrophic factors.