title: Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats.
abstract: Multiple sclerosis (MS) is a debilitating neurodegenerative disease characterized by axonal/neuronal damage that may be caused by defective remyelination. Current therapies aim to slow the rate of degeneration, however there are no treatment options that can stop or reverse the myelin sheath damage. Bone marrow mesenchymal stem cells (MSCs) are a potential candidate for the cell implantation-targeted therapeutic strategies, but the pro-remyelination effects of MSCs when directly injected into a demyelinated cord lesion have been questioned. Neurotrophin-3 (NT-3) has been shown to serve a crucial role in the proliferation, differentiation and maturation of oligodendrocyte lineages. Here, we showed that implantation of NT-3 gene-modified MSCs via a recombinant adenoviral vector (Adv) into a region of ethidium bromide (EB)-induced demyelination in the spinal cord resulted in significant improvement of locomotor function and restoration of electrophysiological properties in rats. The morphological basis of this recovery was evidenced by robust myelin basic protein (MBP) expression and the extensive remyelination. AdvNT-3-MSC implants promote the endogenous remyelinating cells to participate directly in myelination, which was confirmed under light and electron microscopy. Our study suggested that genetically modified MSCs could be a potential therapeutic avenue for improving the efficacy of stem cell treatment for neurodegenerative diseases such as MS.
authors: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. gzjj520@yahoo.com.cn
authors: Yu-Jiao
authors: YJ
authors: Zhang
authors: Wei
authors: W
authors: Zhang
authors: Cheng-Guang
authors: CG
authors: Lin
authors: Ying
authors: Y
authors: Ding
authors: Si-Fan
authors: SF
authors: Huang
authors: Jin-Lang
authors: JL
authors: Wu
authors: Yan
authors: Y
authors: Li
authors: Hongxin
authors: H
authors: Dong
authors: Yuan-Shan
authors: YS
authors: Zeng
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009043:Motor Activity / Q000235:genetics; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D020933:Neurotrophin 3 / Q000008:administration & dosage* / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000235:genetics*; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000601:surgery*; D013904:Thoracic Vertebrae
chemical_list: D004676:Myelin Basic Protein; D020933:Neurotrophin 3