title: Electroacupuncture promotes the differentiation of transplanted bone marrow mesenchymal stem cells overexpressing TrkC into neuron-like cells in transected spinal cord of rats.
abstract: 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.
authors.affiliation: Division of Neuroscience, Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.forename: Qing
authors.initials: Q
authors.lastname: Yan
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Ruan
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Zeng
authors.forename: Si-Fan
authors.initials: SF
authors.lastname: Huang
authors.forename: Yu-Jiao
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Jin-Lang
authors.initials: JL
authors.lastname: Wu
authors.forename: Danny
authors.initials: D
authors.lastname: Fisher
authors.forename: Hongxin
authors.initials: H
authors.lastname: Dong
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zeng
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D015671:Electroacupuncture / Q000379:methods*; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000166:cytology* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D020812:Receptor, trkC / Q000096:biosynthesis*; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000473:pathology / Q000601:surgery / Q000628:therapy*
chemical_list: D020812:Receptor, trkC