title: Highly malignant behavior of a murine oligodendrocyte precursor cell line following transplantation into the demyelinated and nondemyelinated central nervous system.
abstract: Understanding the basic mechanisms that control CNS remyelination is of direct clinical relevance. Suitable model systems include the analysis of naturally occurring and genetically generated mouse mutants and the transplantation of oligodendrocyte precursor cells (OPCs) following experimental  demyelination. However, aforementioned studies were exclusively carried out in rats and little is known about the in vivo behavior of transplanted murine OPCs. Therefore in the present study, we (i) established a model of ethidium bromide-induced demyelination of the caudal cerebellar peduncle  (CCP) in the adult mouse and (ii) studied the distribution and marker expression of the murine OPC line BO-1 expressing the enhanced green fluorescent protein (eGFP) 10 and 17 days after stereotaxic implantation. Injection of ethidium bromide (0.025%) in the CCP resulted in a severe loss of  myelin, marked astrogliosis, and mild to moderate axonal alterations. Transplanted cells formed an invasive and liquorogenic metastasizing tumor, classified as murine giant cell glioblastoma. Transplanted BO-1 cells displayed substantially reduced CNPase expression as compared to their in  vitro phenotype, low levels of MBP and GFAP, prominent upregulation of NG2, PDGFRα, nuclear p53, and an unaltered expression of signal transducer and activator of transcription (STAT)-3. Summarized environmental signaling in the brain stem was not sufficient to trigger oligodendrocytic  differentiation of BO-1 cells and seemed to block CNPase expression. Moreover, the lack of the remyelinating capacity was associated with tumor formation indicating that BO-1 cells may serve as a versatile experimental model to study tumorigenesis of glial tumors.
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Hansmann
authors.forename: Kidsadagon
authors.initials: K
authors.lastname: Pringproa
authors.forename: Reiner
authors.initials: R
authors.lastname: Ulrich
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Sun
authors.forename: Vanessa
authors.initials: V
authors.lastname: Herder
authors.forename: Mihaela
authors.initials: M
authors.lastname: Kreutzer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.forename: Konstantin
authors.initials: K
authors.lastname: Wewetzer
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D004996:Ethidium / Q000633:toxicity; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000637:transplantation; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D004996:Ethidium; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D011509:Proteoglycans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D050796:STAT3 Transcription Factor; D000099216:Chondroitin Sulfate Proteoglycan 4; C485184:enhanced green fluorescent protein