Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, Department of Orthopedics, the Fourth Medical Center, Chinese PLA General Hospital, Beijing 100048, China; Medical School of Chinese PLA, Beijing 100853, China.
Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, Department of Orthopedics, the Fourth Medical Center, Chinese PLA General Hospital, Beijing 100048, China.
Neuroscience. 2023 Aug 1;524:149-157. doi: 10.1016/j.neuroscience.2023.05.029. Epub 2023 Jun 5.
Deferoxamine (DFO) is a potent iron chelator for clinical treatment of various diseases. Recent studies have also shown its potential to promote vascular regeneration during peripheral nerve regeneration. However, the effect of DFO on the Schwann cell function and axon regeneration remains unclear. In this study, we investigated the effects of different concentrations of DFO on Schwann cell viability, proliferation, migration, expression of key functional genes, and axon regeneration of dorsal root ganglia (DRG) through a series of in vitro experiments. We found that DFO improves Schwann cell viability, proliferation, and migration in the early stages, with an optimal concentration of 25 μM. DFO also upregulates the expression of myelin-related genes and nerve growth-promoting factors in Schwann cells, while inhibiting the expression of Schwann cell dedifferentiation genes. Moreover, the appropriate concentration of DFO promotes axon regeneration in DRG. Our findings demonstrate that DFO, with suitable concentration and duration of action, can positively affect multiple stages of peripheral nerve regeneration, thereby improving the effectiveness of nerve injury repair. This study also enriches the theory of DFO promoting peripheral nerve regeneration and provides a basis for the design of sustained-release DFO nerve grafts.
去铁胺（DFO）是一种有效的铁螯合剂，用于临床治疗各种疾病。最近的研究还表明，它具有促进周围神经再生过程中血管再生的潜力。然而，DFO 对施万细胞功能和轴突再生的影响仍不清楚。在这项研究中，我们通过一系列体外实验研究了不同浓度的 DFO 对背根神经节（DRG）施万细胞活力、增殖、迁移、关键功能基因表达和轴突再生的影响。我们发现 DFO 在早期阶段提高了施万细胞的活力、增殖和迁移，最佳浓度为 25 μM。DFO 还上调了施万细胞中髓鞘相关基因和神经生长促进因子的表达，同时抑制了施万细胞去分化基因的表达。此外，适当浓度的 DFO 促进了 DRG 中的轴突再生。我们的研究结果表明，DFO 在适当的浓度和作用时间内，可以积极影响周围神经再生的多个阶段，从而提高神经损伤修复的效果。这项研究也丰富了 DFO 促进周围神经再生的理论，为设计持续释放 DFO 神经移植物提供了依据。
