Combination of electroacupuncture and grafted mesenchymal stem cells overexpressing TrkC improves remyelination and function in demyelinated spinal cord of rats.
Combination of electroacupuncture and grafted mesenchymal stem cells overexpressing TrkC improves remyelination and function in demyelinated spinal cord of rats.
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DOI：
10.1038/srep09133
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发表时间：
2015-03-16
影响因子：
4.6
通讯作者：
Zeng YS
中科院分区：
文献类型：
--
作者：
Ding Y;Zhang RY;He B;Liu Z;Zhang K;Ruan JW;Ling EA;Wu JL;Zeng YS
本研究拟将神经营养素-3（NT-3）受体（TrkC）基因修饰的间充质干细胞（TrkC-MSCs）移植到脱髓鞘脊髓中，观察电针治疗是否能促进脱髓鞘脊髓NT-3分泌，并进一步促进移植的TrkC-MSCs向少突胶质细胞分化、髓鞘再生和功能恢复。于T10脊髓内微量注射溴化乙锭（EB）建立大鼠脱髓鞘模型。实验动物分为六组：假手术组、PBS组、MSC组、MSC +EA组、TrkC-MSC组和TrkC-MSC +EA组。结果显示，TrkC-MSCs移植联合EA处理（TrkC-MSCs+EA组）可显著增加MSCs分化为OPCs和少突胶质样细胞的数量。免疫电镜显示TrkC-MSCs分化为少突胶质细胞样细胞，形成髓鞘。免疫荧光组织化学和Western blot分析表明，TrkC-MSCs+EA处理后，可促进髓鞘碱性蛋白（MBP）表达和Kv 1. 2排列趋向正常水平。此外，行为测试和皮层运动诱发电位检测表明TrkC-MSCs+EA组中的功能恢复显著。总之，我们的研究结果表明，EA治疗可以增加NT-3的表达，促进TrkC-MSCs向少突胶质细胞样细胞分化，促进脱髓鞘脊髓的髓鞘再生和功能改善。
This study attempted to graft neurotrophin-3 (NT-3) receptor (TrkC) gene modified mesenchymal stem cells (TrkC-MSCs) into the demyelinated spinal cord and to investigate whether electroacupuncture (EA) treatment could promote NT-3 secretion in the demyelinated spinal cord as well as further enhance grafted TrkC-MSCs to differentiate into oligodendrocytes, remyelination and functional recovery. Ethidium bromide (EB) was microinjected into the spinal cord of rats at T10 to establish a demyelinated model. Six groups of animals were prepared for the experiment: the sham, PBS, MSCs, MSCs+EA, TrkC-MSCs and TrkC-MSCs+EA groups. The results showed that TrkC-MSCs graft combined with EA treatment (TrkC-MSCs+EA group) significantly increased the number of OPCs and oligodendrocyte-like cells differentiated from MSCs. Immunoelectron microscopy showed that the oligodendrocyte-like cells differentiated from TrkC-MSCs formed myelin sheaths. Immunofluorescence histochemistry and Western blot analysis indicated that TrkC-MSCs+EA treatment could promote the myelin basic protein (MBP) expression and Kv1.2 arrangement trending towards the normal level. Furthermore, behavioural test and cortical motor evoked potentials detection demonstrated a significant functional recovery in the TrkC-MSCs+EA group. In conclusion, our results suggest that EA treatment can increase NT-3 expression, promote oligodendrocyte-like cell differentiation from TrkC-MSCs, remyelination and functional improvement of demyelinated spinal cord.