电针通过NT-3介导炎症调节以促进移植的MSC源性神经网络在损伤脊髓内存活及功能性整合的研究

We successfully constructed the mesenchymal stem cells (MSC)-derived neural network with the function of synaptic transmission in vitro. Although MSC-derived neural network transplanted into the injured spinal cord can reconstruct partly the neural circuits of spinal cord, the continuous inflammatory microenvironment in the injured spinal cord severely interfered with the long-term survival and integration of transplanted neural network cells with the host neural circuits. Our previous results demonstrated that Governor Vessel electron-acupuncture (EA) could promote the neurotrophin-3 (NT-3) secretion of spinal cord tissue to inhibit inflammation and promote the survival of transplanted stem cells in the spinal cord. However, It is unclear how EA regulates inflammation mediated by NT-3 to promote the survival and integration of transplanted neural network with the spinal cord. Therefore, the hypothesis of this study is that: EA simulating meningeal branch of spinal nerve can increase the NT-3 secretion of injured spinal cord tissue, NT-3 mediates local immune cells to secrete anti-inflammatory factor IL-4 which induced proinflammatory cells to transform into anti-inflammatory cells in both sides tissue of transplanted neural network, inhibit inflammation and improve spinal cord injury microenvironment, protect the survival of the MSC neural network cells, and promote better integration of MSC-derived neural network with the host neural circuits and enhance the effect of repairing spinal cord injury. On the basis of our previous work, this study will utilize optogenetics technology to further precisely prove the EA afferent signal pathway which promote the NT-3 secretion of spinal cord and the mechanism of EA anti-inflammation. The study will provide the theory and experimental evidence for clinically applying Governor Vessel electroacupuncture combined tissue engineering neural network transplantation therapy the patient with spinal cord injury.

我们成功构建了具有突触传递功能的间充质干细胞(MSC)源性神经网络，将其移植到脊髓损伤处能部分重建神经环路。但损伤脊髓内持续的炎症反应影响移植神经网络的长期存活及与宿主神经环路的整合。现已证实，督脉电针可通过增强脊髓分泌NT-3，抑制炎症促进移植细胞存活。然而，督脉电针是如何通过NT-3介导炎症调控，促进移植神经网存活的机制尚不明确。因此，本项研究假设：督脉电针刺激脊膜支引起受损脊髓组织分泌NT-3，通过NT-3介导局部免疫细胞分泌抗炎因子IL-4，诱导位于移植神经网络两侧宿主组织内的促炎细胞向抗炎细胞转化，抑制炎症反应，改善脊髓损伤区微环境，保护MSC源性神经网络细胞并促进其与宿主脊髓神经环路更好地整合，提高修复脊髓损伤的效果。本研究将在前期工作基础上利用光遗传学等技术精准探明督脉电针促进脊髓NT-3分泌及其抗炎机制，为临床应用督脉电针联合组织工程神经网络修复脊髓损伤提供理论和实验依据。