title: Transplanted miR-219-overexpressing oligodendrocyte precursor cells promoted remyelination and improved functional recovery in a chronic demyelinated model.
abstract: Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4. MiR-219 accelerated the differentiation of mESC-derived neural precursor cells (NPCs) into OPCs. We further transplanted OPCs derived from miR219-mESCs (miR219-OPCs) into cuprizone-induced chronically demyelinated mice to observe remyelination, which resulted in well-contained oligodendrocyte grafts that migrated along the corpus callosum and matured to express myelin basic protein (MBP). Ultrastructural studies further confirmed the presence of new myelin sheaths. Improved cognitive function in these mice was confirmed by behavioral tests. Importantly, the transplanted miR219-OPCs induced the proliferation of endogenous NPCs. In conclusion, these data demonstrate that miR-219 rapidly transforms mESCs into oligodendrocyte lineage cells and that the transplantation of miR219-OPCs not only promotes remyelination and improves cognitive function but also enhances the proliferation of host endogenous NPCs following chronic demyelination. These results support the potential of a therapeutic role for miR-219 in demyelinating diseases.
authors.affiliation: Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221009, China.|Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Fan
authors.affiliation: Clinical Laboratory, Xuzhou Center Hospital, Xuzhou, 221000, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Chen
authors.affiliation: Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221009, China.
authors.forename: Xue-Bin
authors.initials: XB
authors.lastname: Qu
authors.affiliation: Department of Laboratory, No. 100 Hospital of CPLA, Suzhou, 215007, China.
authors.forename: Chuan-Lu
authors.initials: CL
authors.lastname: Ren
authors.affiliation: Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221009, China.
authors.forename: Xiu-Xiang
authors.initials: XX
authors.lastname: Wu
authors.affiliation: Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221009, China.
authors.forename: Fu-Xing
authors.initials: FX
authors.lastname: Dong
authors.affiliation: Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221009, China.
authors.forename: Bao-Le
authors.initials: BL
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221009, China.
authors.forename: Dian-Shuai
authors.initials: DS
authors.lastname: Gao
authors.affiliation: Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221009, China.
authors.forename: Rui-Qin
authors.initials: RQ
authors.lastname: Yao
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D002908:Chronic Disease; D018920:Coculture Techniques; D003072:Cognition Disorders / Q000503:physiopathology / Q000628:therapy; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000235:genetics* / Q000503:physiopathology*; D004195:Disease Models, Animal; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000073637:Oligodendrocyte Precursor Cells / Q000637:transplantation*; D039904:Pluripotent Stem Cells / Q000378:metabolism; D020127:Recovery of Function; D000074586:Remyelination / Q000235:genetics*
chemical_list: C000609357:MIRN219 microRNA, mouse; D035683:MicroRNAs; D003471:Cuprizone