Oligodendrocyte progenitor cell (OPC) transplantation is unlikely to offer a means of preventing X-irradiation induced damage in the CNS.
Oligodendrocyte lineage cells [oligodendrocytes and their parent cells, the oligodendrocyte progenitor cells (OPCs)] are depleted by X-irradiation and progenitor cell transplantation has been proposed as a therapeutic strategy to counteract radiation induced myelopathy. Previous studies have demonstrated that oligodendrocyte progenitor cell (OPC) depletion is a prerequisite for establishing transplanted OPCs in normal tissue. One can therefore predict that the extent and timing of OPC depletion and regeneration following X-irradiation will be crucial factors in determining the feasibility of this therapeutic approach. To address this issue, we have examined the time course of OPC depletion and regeneration following a range of X-irradiation doses (5 to 40 Gy), and its relationship to establishing transplanted OPCs in X-irradiated tissue. Doses above 10 Gy resulted in rapid death of OPCs. With doses up to 20 Gy, surviving X-irradiated OPCs were capable of robust regeneration, restoring normal densities within 6 weeks. Transplanted OPCs could only be established in tissue that had been exposed to > or =20 Gy. Since 20 Gy is close to the ED50 for radiation necrosis, our findings demonstrate the limitation of OPC replacement strategies.
Chari
Divya M
DM
Cambridge Centre for Brain Repair and Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK. dmc35@hermes.cam.ac.uk
Gilson
Jennifer M
JM
Franklin
Robin J M
RJ
Blakemore
William F
WF
D000818:Animals; D000941:Antigens / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002493:Central Nervous System Diseases / Q000209:etiology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D017403:In Situ Hybridization / Q000379:methods; D007211:Indoles; D008297:Male; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000502:physiology / Q000637:transplantation*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D014965:X-Rays / Q000009:adverse effects*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D053148:Caspase 3; D020169:Caspases; D007211:Indoles; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C489071:Plp1 protein, rat; C007293:DAPI; C505410:Casp3 protein, rat