Combination of Electroacupuncture and Grafted Mesenchymal Stem Cells Overexpressing TrkC Improves Remyelination and Function in Demyelinated Spinal Cord of Rats

被引:40
作者
Ding, Ying [1 ]
Zhang, Rong-Yi [1 ]
He, Bing [1 ]
Liu, Zhou [1 ]
Zhang, Ke [1 ]
Ruan, Jing-Wen [5 ]
Ling, Eng-Ang [6 ]
Wu, Jin-Lang [7 ]
Zeng, Yuan-Shan [1 ,2 ,3 ,4 ]
机构
[1] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Histol & Embryol, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Key Lab Stem Cells & Tissue Engn, Minist Educ, Guangzhou 510080, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Inst Spinal Cord Injury, Guangzhou 510127, Guangdong, Peoples R China
[4] Univ Nantong, Coinnovat Ctr Neuroregenerat, Nantong 226011, Jiangsu, Peoples R China
[5] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Acupuncture, Guangzhou 510080, Guangdong, Peoples R China
[6] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, Singapore 117595, Singapore
[7] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Electron Microscope, Guangzhou 510080, Guangdong, Peoples R China
基金
中国国家自然科学基金; 中央高校基本科研业务费专项资金资助;
关键词
MYELIN OLIGODENDROCYTE GLYCOPROTEIN; MULTIPLE-SCLEROSIS; NERVOUS-SYSTEM; NEUROTROPHIN EXPRESSION; ANIMAL-MODELS; STROMAL CELLS; IN-VITRO; CNS; TRANSPLANTATION; INJURY;
D O I
10.1038/srep09133
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
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页数:14
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