Electroacupuncture Promotes the Differentiation of Transplanted Bone Marrow Mesenchymal Stem Cells Overexpressing TrkC Into Neuron-Like Cells in Transected Spinal Cord of Rats
Electroacupuncture Promotes the Differentiation of Transplanted Bone Marrow Mesenchymal Stem Cells Overexpressing TrkC Into Neuron-Like Cells in Transected Spinal Cord of Rats
复制标题
电针促进过表达TrkC的移植骨髓间充质干细胞分化为大鼠脊髓横断神经元样细胞
DOI：
10.3727/096368912x655037
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Zeng, Yuan-Shan
中科院分区：
文献类型：
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作者：
Ding, Ying;Yan, Qing;Zeng, Yuan-Shan
我们先前的研究表明，电针可以提高损伤脊髓中神经营养素-3(NT-3)的水平，刺激移植的骨髓间充质干细胞(MSCs)的分化，促进损伤脊髓的功能恢复。然而，骨髓间充质干细胞来源的神经元样细胞数量有限。已知NT-3通过优先与其受体TrkC结合来促进神经元的存活和分化。在本研究中，我们试图将TrkC基因修饰的MSCs(TrkC-MSCs)横断移植到脊髓内，以观察电针治疗是否能促进损伤脊髓中NT-3的分泌，以及增加NT-3是否能进一步促进移植的高表达TrkC的MSCs分化为神经元样细胞，从而增加损伤脊髓的轴突再生和功能改善。结果表明，电针可提高移植的TrkC-MSCs的NT-3水平，促进神经表型分化、突触形成和髓鞘形成。此外，TrkC-MSC移植联合电针治疗(TrkC-MSCs+电针组)可促进BDA标记的皮质脊髓束(CST)的生长和5-羟色胺(5-HT)阳性轴突穿过损伤部位进入尾侧脊髓。此外，与对照组(LacZ-MSCs组、TrkC-MSCs组和LacZ-MSCs+EA组)相比，皮质运动诱发电位(MEP)的传导和后肢运动功能增强。在TrkC-MSCs+电针组，损伤脊髓中神经源性因子LN和GAP-43表达上调，而轴突生长的主要抑制因子GFAP和硫酸软骨素蛋白多糖(CSPGs)表达下调。综上所述，我们的数据表明，TrkC-MSC移植联合电针治疗脊髓损伤不仅能增加MSC的存活和向神经元样细胞的分化，而且还能促进CST跨损伤部位的再生和功能改善，这可能是由于NT-3水平增加，层粘连蛋白和GAP-43上调，GFAP和CSPG蛋白下调所致。
Our previous study indicated that electroacupuncture (EA) could increase neurotrophin-3 (NT-3) levels in the injured spinal cord, stimulate the differentiation of transplanted bone marrow mesenchymal stem cells (MSCs), and improve functional recovery in the injured spinal cord of rats. However, the number of neuron-like cells derived from the MSCs is limited. It is known that NT-3 promotes the survival and differentiation of neurons by preferentially binding to its receptor TrkC. In this study, we attempted to transplant TrkC gene-modified MSCs (TrkC-MSCs) into the spinal cord with transection to investigate whether EA treatment could promote NT-3 secretion in the injured spinal cord and to determine whether increased NT-3 could further enhance transplanted MSCs overexpressing TrkC to differentiate into neuron-like cells, resulting in increased axonal regeneration and functional improvement in the injured spinal cord. Our results showed that EA increased NT-3 levels; furthermore, it promoted neuron-phenotype differentiation, synaptogenesis, and myelin formation of transplanted TrkC-MSCs. In addition, TrkC-MSC transplantation combined with EA (the TrkC-MSCs + EA group) treatment promoted the growth of the descending BDA-labeled corticospinal tracts (CSTs) and 5-HT-positive axonal regeneration across the lesion site into the caudal cord. In addition, the conduction of cortical motor-evoked potentials (MEPs) and hindlimb locomotor function increased as compared to controls (treated with the LacZ-MSCs, TrkC-MSCs, and LacZ-MSCs + EA groups). In the TrkC-MSCs + EA group, the injured spinal cord also showed upregulated expression of the proneurogenic factors laminin and GAP-43 and downregulated GFAP and chondroitin sulfate proteoglycans (CSPGs), major inhibitors of axonal growth. Together, our data suggest that TrkC-MSC transplantation combined with EA treatment spinal cord injury not only increased MSC survival and differentiation into neuron-like cells but also promoted CST regeneration across injured sites to the caudal cord and functional improvement, perhaps due to increase of NT-3 levels, upregulation of laminin and GAP-43, and downregulation of GFAP and CSPG proteins.