GDNF preconditioning can overcome Schwann cell phenotypic memory.
GDNF preconditioning can overcome Schwann cell phenotypic memory.
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DOI：
10.1016/j.expneurol.2014.12.003
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发表时间：
2015-03
影响因子：
5.3
通讯作者：
Sakiyama-Elbert, Shelly E.
中科院分区：
文献类型：
--
作者：
Marquardt, Laura M.;Sakiyama-Elbert, Shelly E.
关键词：
虽然已知许旺细胞（SC）提供了增强周围神经损伤后再生的线索，但SC表型记忆（肌肉或皮神经来源）对增强轴突再生和功能恢复的影响在文献中尚不清楚。特别是，肌肉和皮肤神经源性SC之间的差异可能会鼓励特定的运动或感觉轴突的细胞/组织移植治疗的指导。因此，本研究的目的是确定与不匹配的组合（即运动神经元/肌肉神经源性SC与运动神经元/皮肤神经源性SC）相比，神经元和SC的表型匹配组合是否刺激更大的轴突延伸。此外，还评价了胶质细胞源性神经营养因子（GDNF）治疗对SC-神经元相互作用的影响。为了研究这些相互作用，使用微流控装置来评估SC分泌的可溶性因子对神经元的影响。与传统的共培养方法不同，该设备允许在长时间内更容易地量化单个神经突延伸，以及简单地对纯群体进行细胞和培养基取样以进行生化分析。结果表明，当神经元与表型匹配的SC一起培养时，神经突生长时间更长，这表明SC能够保留表型记忆，尽管长时间没有轴突接触。此外，当用GDNF预处理错配的SC时，可以克服错配培养物的负面影响。这些结果表明，用GDNF处理SC可以增强其通过临床上经常使用的不匹配移植物促进再生的能力。
While it is known that Schwann cells (SCs) provide cues to enhance regeneration following peripheral nerve injury, the effect of SC phenotypic memory (muscle or cutaneous nerve-derived) on enhancing axonal regeneration and functional recovery has been unclear in the literature. In particular, differences between muscle and cutaneous nerve-derived SC may encourage specific motor or sensory axonal guidance in cell/tissue transplantation therapies. Thus, the goal of this study was to determine whether phenotypically matched combinations of neurons and SCs stimulate greater axonal extension compared to mismatched combinations (i.e. motor neurons/muscle nerve-derived SCs vs. motor neurons/cutaneous nerve-derived SCs). Additionally, the effect of glial cell line-derived neurotrophic factor (GDNF) treatment on SC-neuron interaction was also evaluated. In order to examine these interactions, microfluidic devices were used to assess the effects of soluble factors secreted from SCs on neurons. Unlike traditional co-culture methods, the devices allow for easier quantification of single neurite extension over long periods of time, as well as easy cell and media sampling of pure populations for biochemical analyses. Results demonstrated longer neurite growth when neurons are cultured with phenotype matched SCs, suggesting that SCs are capable of retaining phenotypic memory despite a prolonged absence of axonal contact. Furthermore, the negative effect of mismatched cultures can be overcome when mismatched SCs are preconditioned with GDNF. These results suggest that treatment of SCs with GDNF could enhance their ability to promote regeneration through mismatched grafts frequently used in clinical settings.
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Sakiyama-Elbert, Shelly E.
影响因子：
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通讯作者：
Sakiyama-Elbert, Shelly E.