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Local Delivery of Epigenetically Stimulating Folic Acid For Peripheral Nerve Regeneration

机译:表观遗传刺激叶酸的局部递送,用于周围神经再生

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We report that folic acid is an inexpensive and multifunctional niche component that modulates behaviors in different cells in the nervous system. The multiple benefits of modulation include: 1) generating chemotactic responses on glial cells, 2) inducing neurotrophin release, and 3) stimulating neuronal differentiation of a PC-12 cell system. For the first time, folic acid is also shown to enhance cellular force generation and global methylation in the PC-12 cells, thereby enabling both biomechanical and biochemical pathways to regulate neuron differentiation. These findings are evaluated in vivo for clinical translation. Our results suggest that the epigenetically stimulating folic acid-nerve guidance conduits may offer significant benefits as a low-cost, off-the-shelf product for reaching the functional recovery seen with autografts in large sciatic nerve defects.
机译:我们报告说,叶酸是一种廉价且多功能的利基成分,可调节神经系统中不同细胞的行为。调节的多重好处包括:1)在神经胶质细胞上产生趋化反应,2)诱导神经营养蛋白释放,和3)刺激PC-12细胞系统的神经元分化。叶酸还首次显示出可增强PC-12细胞中细胞力的产生和整体甲基化,从而使生物力学和生化途径均能调节神经元的分化。对这些发现进行体内评估以进行临床翻译。我们的研究结果表明,表观遗传刺激叶酸神经引导导管作为一种低成本,现成的产品,可以提供巨大的好处,可实现自体移植在坐骨神经大缺损中所见的功能恢复。

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