title: Combination of electroacupuncture and grafted mesenchymal stem cells overexpressing TrkC improves remyelination and function in demyelinated spinal cord of rats.
abstract: 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.
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Rong-Yi
authors.initials: RY
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Acupuncture, the 1st Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Ruan
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.affiliation: Department of Electron Microscope, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Jin-Lang
authors.initials: JL
authors.lastname: Wu
authors.affiliation: 1] Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [2] Key Laboratory for Stem Cells and Tissue Engineering Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [3] Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, Guangdong 510127, China [4] Co-innovation Center of Neuroregeneration, University, Nantong, Nantong, Jiangsu 226011, China.
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zeng
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D003711:Demyelinating Diseases / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D004195:Disease Models, Animal; D015671:Electroacupuncture; D019054:Evoked Potentials, Motor; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D051381:Rats; D020812:Receptor, trkC / Q000235:genetics* / Q000378:metabolism; D020127:Recovery of Function; D013118:Spinal Cord Diseases / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: D020933:Neurotrophin 3; D020812:Receptor, trkC