The adult central nervous system (CNS) possesses a limited capacity for self-repair. Severed CNS axons typically fail to regrow. There is an unmet need for treatments designed to enhance neuronal viability, facilitate axon regeneration and ultimately restore lost neurological functions to individuals affected by traumatic CNS injury, multiple sclerosis, stroke and other neurological disorders. Here we demonstrate that both mouse and human bone marrow neutrophils, when polarized with a combination of recombinant interleukin-4 (IL-4) and granulocyte colony-stimulating factor (G-CSF), upregulate alternative activation markers and produce an array of growth factors, thereby gaining the capacity to promote neurite outgrowth. Moreover, adoptive transfer of IL-4/G-CSF-polarized bone marrow neutrophils into experimental models of CNS injury triggered substantial axon regeneration within the optic nerve and spinal cord. These findings have far-reaching implications for the future development of autologous myeloid cell-based therapies that may bring us closer to effective solutions for reversing CNS damage.

成人中枢神经系统（CNS）的自我修复能力有限。切断的中枢神经系统轴突通常无法再生。对于旨在增强神经元活力、促进轴突再生并最终恢复受创伤性中枢神经系统损伤、多发性硬化症、中风和其他神经系统疾病影响的个体失去的神经功能的治疗的需求尚未得到满足。在这里，我们证明，当用重组白细胞介素 4 (IL-4) 和粒细胞集落刺激因子 (G-CSF) 组合极化时，小鼠和人类骨髓中性粒细胞会上调替代激活标记物并产生一系列生长因子，从而获得促进神经突生长的能力。此外，将IL-4/G-CSF极化的骨髓中性粒细胞过继转移到中枢神经系统损伤的实验模型中，引发了视神经和脊髓内的大量轴突再生。这些发现对基于自体骨髓细胞的疗法的未来发展具有深远的影响，可能使我们更接近逆转中枢神经系统损伤的有效解决方案。