Porcine neural progenitors require commitment to the oligodendrocyte lineage prior to transplantation in order to achieve significant remyelination of demyelinated lesions in the adult CNS.
Glial cell transplantation is a potential therapy for human demyelinating disease, though obtaining large numbers of oligodendrocyte precursors from nonrodent species is currently problematic. Culturing of multipotent neural progenitors may provide a solution to this problem, because these cells can be expanded in vitro whilst retaining the ability to differentiate into both neurons and glial cells. In order to investigate the myelinating capability of multipotent neural progenitors, we isolated cells from the porcine subventricular zone, a region rich in neural progenitors, and transplanted them into areas of persistent demyelination in the spinal cord of immunosuppressed rats, created by the injection of ethidium bromide and subsequent exposure to 40 Gy X-irradiation. Porcine SVZ cells were transplanted either within 12 h of isolation or after 7 days in B104-conditioned medium. Freshly isolated cells did not mature into myelinating oligodendrocytes following transplantation and instead remained as clusters of undifferentiated progenitors. However, cells exposed to B104-conditioned medium prior to transplantation were able to effect complete remyelination of the demyelinated axons. This suggests that neural progenitors must be manipulated in vitro for commitment to the oligodendrocyte lineage prior to transplantation if significant remyelination is to be achieved.
Smith
P M
PM
Department of Clinical Veterinary Medicine, University of Cambridge, UK. pms24@hermes.cam.ac.uk
Blakemore
W F
WF
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000601:surgery; D005260:Female; D007165:Immunosuppression Therapy; D008854:Microscopy, Electron; D009413:Nerve Fibers, Myelinated / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000637:transplantation* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology / Q000601:surgery*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D013552:Swine
D017077:Culture Media, Conditioned