Injury-activated endogenous neural stem cells (NSCs) in the spinal cord have promising therapeutic applications for rebuilding the neuronal relays after spinal cord injury (SCI) because of their lack of immune-rejection following exogenous cell transplantation. However, these NSCs rarely differentiate into neurons and the damaged axonal regenerative ability is drastically reduced due to the adverse SCI microenvironment. Cetuximab, an EGFR signaling antagonist, has demonstrated the ability of promoting NSC differentiation into neurons. Taxol, in addition to stabilizing microtubules, has shown potential for enhancing axonal regeneration and reducing scar formation after SCI. In this study, we further verified the combined therapeutic effects of Cetuximab and Taxol on inhibition of scar deposition and promotion of neuronal differentiation, axonal outgrowth and functional recovery in a rat severe SCI model. A linear orderly collagen scaffold modified with Cetuximab and Taxol was grafted into the SCI site after the complete removal of 4 mm of spinal tissue. The results showed that the combined functional scaffold implantation significantly increased neural regeneration to reconnect the neural network. Moreover, scaffold transplantation decreases the deposition of varied scar-related inhibitors within the lesion center, further reflecting the need for a combination dedicated to increasing motor function following SCI. Collagen scaffold based-combined therapy provides a potential strategy for improving functional restoration of the injured spinal cord.

中文翻译：

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西妥昔单抗和紫杉醇共修饰的胶原蛋白支架显示出联合作用，可修复急性脊髓损伤†

脊髓中的损伤激活内源性神经干细胞（NSC）由于在外源细胞移植后缺乏免疫排斥反应，因此有望在重建脊髓损伤（SCI）后的神经元中继物中具有广阔的治疗应用前景。但是，这些NSC很少分化为神经元，并且由于不利的SCI微环境，受损的轴突再生能力会大大降低。西妥昔单抗是一种EGFR信号传导拮抗剂，已证明具有促进NSC分化为神经元的能力。除稳定微管外，紫杉酚还显示出增强SCI后轴突再生和减少疤痕形成的潜力。在这项研究中，我们进一步验证了西妥昔单抗和紫杉醇对抑制疤痕沉积和促进神经元分化的联合治疗作用，在大鼠严重SCI模型中轴突生长和功能恢复。在完全切除4毫米的脊髓组织后，将用西妥昔单抗和紫杉醇修饰的线性有序胶原支架移植到SCI部位。结果表明，组合功能支架植入显着增加了神经再生，从而重新连接了神经网络。此外，支架移植减少了病变中心内各种与疤痕相关的抑制剂的沉积，进一步反映了需要一种专门用于增加SCI后运动功能的组合的需求。基于胶原蛋白支架的联合疗法为改善受损脊髓的功能恢复提供了潜在的策略。在完全切除4毫米的脊髓组织后，将用西妥昔单抗和紫杉醇修饰的线性有序胶原支架移植到SCI部位。结果表明，组合功能支架植入显着增加了神经再生，从而重新连接了神经网络。此外，支架移植减少了病变中心内各种与疤痕相关的抑制剂的沉积，进一步反映了需要一种专门用于增加SCI后运动功能的组合的需求。基于胶原蛋白支架的联合疗法为改善受损脊髓的功能恢复提供了潜在的策略。在完全切除4毫米的脊髓组织后，将用西妥昔单抗和紫杉醇修饰的线性有序胶原支架移植到SCI部位。结果表明，组合功能支架植入显着增加了神经再生，从而重新连接了神经网络。此外，支架移植减少了病变中心内各种与疤痕相关的抑制剂的沉积，进一步反映了需要一种专门用于增加SCI后运动功能的组合的需求。基于胶原蛋白支架的联合疗法为改善受损脊髓的功能恢复提供了潜在的策略。结果表明，组合功能支架植入显着增加了神经再生，从而重新连接了神经网络。此外，支架移植减少了病变中心内各种与疤痕相关的抑制剂的沉积，进一步反映了需要一种专门用于增加SCI后运动功能的组合的需求。基于胶原蛋白支架的联合疗法为改善受损脊髓的功能恢复提供了潜在的策略。结果表明，组合功能支架植入显着增加了神经再生，从而重新连接了神经网络。此外，支架移植减少了病变中心内各种与疤痕相关的抑制剂的沉积，进一步反映了需要一种专门用于增加SCI后运动功能的组合的需求。基于胶原蛋白支架的联合疗法为改善受损脊髓的功能恢复提供了潜在的策略。