Electroacupuncture facilitates the integration of a grafted TrkC-modified mesenchymal stem cell-derived neural network into transected spinal cord in rats via increasing neurotrophin-3.

This study was aimed to investigate whether electroacupuncture (EA) would increase the secretion of neurotrophin‐3 (NT‐3) from injured spinal cord tissue, and, if so, whether the increased NT‐3 would promote the survival, differentiation, and migration of grafted tyrosine kinase C (TrkC)‐modified mesenchymal stem cell (MSC)‐derived neural network cells. We next sought to determine if the latter would integrate with the host spinal cord neural circuit to improve the neurological function of injured spinal cord. After NT‐3‐modified Schwann cells (SCs) and TrkC‐modified MSCs were co‐cultured in a gelatin sponge scaffold for 14 days, the MSCs differentiated into neuron‐like cells that formed a MSC‐derived neural network (MN) implant. On this basis, we combined the MN implantation with EA in a rat model of spinal cord injury (SCI) and performed immunohistochemical staining, neural tracing, electrophysiology, and behavioral testing after 8 weeks. Electroacupuncture application enhanced the production of endogenous NT‐3 in damaged spinal cord tissues. The increase in local NT‐3 production promoted the survival, migration, and maintenance of the grafted MN, which expressed NT‐3 high‐affinity TrkC. The combination of MN implantation and EA application improved cortical motor‐evoked potential relay and facilitated the locomotor performance of the paralyzed hindlimb compared with those of controls. These results suggest that the MN was better integrated into the host spinal cord neural network after EA treatment compared with control treatment. Electroacupuncture as an adjuvant therapy for TrkC‐modified MSC‐derived MN, acted by increasing the local production of NT‐3, which accelerated neural network reconstruction and restoration of spinal cord function following SCI. A schematic diagram showing that MSC‐derived neural network is better integrated with the host spinal cord neural network after the EA treatment.

本研究旨在探讨电针（EA）是否会增加受损脊髓组织中神经营养因子 - 3（NT - 3）的分泌，如果是，增加的NT - 3是否会促进移植的酪氨酸激酶C（TrkC）修饰的间充质干细胞（MSC）衍生的神经网络细胞的存活、分化和迁移。我们接下来试图确定后者是否会与宿主脊髓神经回路整合以改善受损脊髓的神经功能。 在将NT - 3修饰的雪旺细胞（SCs）和TrkC修饰的MSCs在明胶海绵支架中共培养14天后，MSCs分化为神经元样细胞，形成了MSC衍生的神经网络（MN）移植物。在此基础上，我们在脊髓损伤（SCI）大鼠模型中将MN移植与EA相结合，并在8周后进行免疫组织化学染色、神经追踪、电生理学和行为学测试。 电针应用增强了受损脊髓组织中内源性NT - 3的产生。局部NT - 3产生的增加促进了移植的MN的存活、迁移和维持，MN表达NT - 3高亲和力TrkC。与对照组相比，MN移植和EA应用相结合改善了皮质运动诱发电位传导，并促进了瘫痪后肢的运动能力。这些结果表明，与对照治疗相比，EA治疗后MN更好地整合到宿主脊髓神经网络中。 电针作为TrkC修饰的MSC衍生的MN的辅助疗法，通过增加NT - 3的局部产生来发挥作用，从而加速了SCI后神经网络的重建和脊髓功能的恢复。 示意图显示在EA治疗后MSC衍生的神经网络更好地与宿主脊髓神经网络整合。