Tammia Markus, Mi Ruifa, Sluch Valentin M, Zhu Allen, Chung Tiffany, Shinn Daniel, Zack Donald J, Höke Ahmet, Mao Hai-Quan
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Heliyon. 2018 Nov 29;4(11):e00982. doi: 10.1016/j.heliyon.2018.e00982. eCollection 2018 Nov.
Schwann cells are key players in peripheral nerve regeneration, and are uniquely capable of remyelinating axons in this context. Schwann cells orchestrate this process via a set of transcription factors. While it has been shown that overexpression of specific genes, upregulates myelin-related transcripts, it remains unknown if such manipulation can functionalize the cells and enhance their myelination frequency. The ability to do so could have implications in the use of human stem cell-derived Schwann cells, where myelination is hard to achieve. After screening four candidate transcription factors ( and ), we found that overexpression of in rat Schwann cells co-cultured with sensory neurons enhanced myelination frequency and reduced cell proliferation. However, in a mouse model of sciatic nerve repair with cells engrafted within a nerve guide, myelination frequency in the engrafted cells was reduced upon overexpression. Our results show that while overexpression of can enhance the myelination frequency , it is context-dependent, potentially influenced by the microenvironment, timing of association with axons, expression level, species differences, or other factors.
施万细胞是周围神经再生的关键参与者，并且在这种情况下具有独特的重新髓鞘化轴突的能力。施万细胞通过一组转录因子协调这一过程。虽然已经表明特定基因的过表达会上调髓鞘相关转录本，但这种操作是否能使细胞功能化并提高其髓鞘化频率仍不清楚。这样做的能力可能对使用人类干细胞衍生的施万细胞有影响，因为在这种细胞中很难实现髓鞘化。在筛选了四种候选转录因子（和）后，我们发现与感觉神经元共培养的大鼠施万细胞中过表达会提高髓鞘化频率并减少细胞增殖。然而，在坐骨神经修复的小鼠模型中，将细胞植入神经导管后，过表达会降低植入细胞的髓鞘化频率。我们的结果表明，虽然过表达可以提高髓鞘化频率，但这取决于具体情况，可能受到微环境、与轴突关联的时间、表达水平、物种差异或其他因素的影响。
