The remyelinating potential and in vitro differentiation of MOG-expressing oligodendrocyte precursors isolated from the adult rat CNS.
There is a long-standing controversy as to whether oligodendrocytes may be capable of cell division and thus contribute to remyelination. We recently published evidence that a subpopulation of myelin oligodendrocyte glycoprotein (MOG)-expressing cells in the adult rat spinal cord co-expressed molecules previously considered to be restricted to oligodendrocyte progenitors [G. Li et al. (2002) Brain Pathol., 12, 463-471]. To further investigate the properties of MOG-expressing cells, anti-MOG-immunosorted cells were grown in culture and transplanted into acute demyelinating lesions. The immunosorting protocol yielded a cell preparation in which over 98% of the viable cells showed anti-MOG- and O1-immunoreactivity; 12-15% of the anti-MOG-immunosorted cells co-expressed platelet-derived growth factor alpha receptor (PDGFRalpha) or the A2B5-epitope. When cultured in serum-free medium containing EGF and FGF-2, 15-18% of the anti-MOG-immunosorted cells lost anti-MOG- and O1-immunoreactivity and underwent cell division. On removal of these growth factors, cells differentiated into oligodendrocytes, or astrocytes and Schwann cells when the differentiation medium contained BMPs. Transplantation of anti-MOG-immunosorted cells into areas of acute demyelination immediately after isolation resulted in the generation of remyelinating oligodendrocytes and Schwann cells. Our studies indicate that the adult rat CNS contains a significant number of oligodendrocyte precursors that express MOG and galactocerebroside, molecules previously considered restricted to mature oligodendrocytes. This may explain why myelin-bearing oligodendrocytes were considered capable of generating remyelinating cells. Our study also provides evidence that the adult oligodendrocyte progenitor can be considered as a source of the Schwann cells that remyelinate demyelinated CNS axons following concurrent destruction of oligodendrocytes and astrocytes.
Crang
A J
AJ
Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, UK.
Gilson
J M
JM
Li
W-W
WW
Blakemore
W F
WF
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D001562:Benzimidazoles / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology*; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000628:therapy; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004996:Ethidium; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism; D017348:Microscopy, Electron, Scanning Transmission / Q000379:methods; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D050816:Octamer Transcription Factor-6; D009836:Oligodendroglia / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019737:Transplants
D001562:Benzimidazoles; D019485:Bone Morphogenetic Proteins; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; C494179:Pou3f1 protein, rat; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6; D004815:Epidermal Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D021983:Cyclophilins; D004996:Ethidium; D001973:Bromodeoxyuridine; C017807:bisbenzimide ethoxide trihydrochloride