title: ES cell-derived glial precursors contribute to remyelination in acutely demyelinated spinal cord lesions.
abstract: Pluripotent embryonic stem (ES) cells have emerged as a powerful tool for disease modeling and neural regeneration. Transplantation studies in rodents indicate that ES cell-derived glial precursors (ESGPs) efficiently restore myelin in dysmyelinating mutants and chemically induced foci of myelin loss. Here we explore the myelination potential of ESGPs in an antibody/complement-induced demyelination model. Microinjection of an antibody to myelin oligodendrocyte glycoprotein (MOG) and complement was employed to generate circumscribed areas of demyelination in the adult rat spinal cord. ESGPs transplanted into 2-day-old lesions were found to survive and differentiate into both oligodendrocytes and astrocytes. The engrafted cells remained largely confined to the lesion site and showed no evidence of tumor formation up until 4 weeks after transplantation. Within areas of pronounced microglial activation and macrophage extravasation, engrafted ES cell-derived oligodendrocytes contacted and enwrapped host axons and alongside endogenous glia, contributed to the formation of new myelin sheaths. These findings demonstrate that ESGPs transplanted into acutely demyelinated lesions can contribute to myelin repair.
authors.affiliation: Institute of Reconstructive Neurobiology, University of Bonn LIFE & BRAIN Center, Bonn, Germany.
authors.forename: Alberto
authors.initials: A
authors.lastname: Perez-Bouza
authors.forename: Tamara
authors.initials: T
authors.lastname: Glaser
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
mesh_terms: D000818:Animals; D000906:Antibodies / Q000633:toxicity; D002454:Cell Differentiation; D003711:Demyelinating Diseases / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000473:pathology*; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000648:ultrastructure; D051381:Rats; D013116:Spinal Cord / Q000473:pathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
chemical_list: D000906:Antibodies; C571327:Mog protein, mouse; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein