Minimally manipulated oligodendrocyte precursor cells retain exclusive commitment to the oligodendrocyte lineage following transplantation into intact and injured hippocampus.
Oligodendrocyte precursor cells (OPCs) are widely regarded as the best characterized cell population in the mammalian CNS and until recently were believed to be a lineage-restricted precursor terminally differentiating to postmitotic oligodendrocytes. Recent evidence has suggested that OPCs may have in vitro and in vivo neuronal potential. In this report we examine the differentiation potential of cortical OPC populations following transplantation into the neurogenic environment of the intact neonatal and adult hippocampus. Donor OPCs were minimally manipulated and not subjected to long-term ex vivo manipulation such as expansion or treatment with mitogens. Minimally manipulated OPCs did not exhibit any intrinsic neuronal potential in vitro prior to transplantation. Following transplantation of GFP-OPCs into intact neonatal and adult hippocampus, cells were able to survive and integrate for at least 14 weeks but did not exhibit neuronal differentiation. Induction of a focal neurotoxic lesion also did not result in neuronal differentiation of graft-derived OPCs. These findings show that unselected and unmanipulated populations of cortical OPCs remain as precursor cells, commit to the oligodendrocyte lineage and fail to respond to the extrinsic cues of a neurogenic or injured environment.
Webber
Daniel J
DJ
Department of Clinical Neurosciences and Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 2PY, UK. djw74@cam.ac.uk
Compston
Alastair
A
Chandran
Siddharthan
S
D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001930:Brain Injuries / Q000473:pathology* / Q000601:surgery; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000601:surgery*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*
D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins