title: Intraventricular transplantation of oligodendrocyte progenitors into a fetal myelin mutant results in widespread formation of myelin.
abstract: Transplantation of myelin-forming cells is a promising strategy for the treatment of myelin disorders. In this study, transplantation of glial cell progenitors into the cerebral ventricles of the embryonic myelin-deficient rat, a model of Pelizaeus-Merzbacher disease, was performed to assess the ability of these cells to incorporate into the developing brain and produce myelin. The donor cells migrated into the white and gray matter and produced myelin at widespread sites ranging from the corpus callosum and optic nerve to the cerebellum. These data suggest that myelin repair might be achieved by intraventricular delivery and transependymal incorporation of myelin-producing cells. Because these cells were genetically transduced to express a reporter gene, similar ex vivo manipulation with genes known to promote survival, migration, or proliferation of the transplanted cells could be used to enhance repair. Such a therapeutic strategy may be feasible in patients with inherited myelin disorders or in multiple sclerosis, particularly where the lesions are periventricular.
authors.affiliation: University of Wisconsin, School of Veterinary Medicine, Madison 53706, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Learish
authors.forename: O
authors.initials: O
authors.lastname: Brüstle
authors.forename: S C
authors.initials: SC
authors.lastname: Zhang
authors.forename: I D
authors.initials: ID
authors.lastname: Duncan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016380:Brain Tissue Transplantation / Q000502:physiology*; D017690:Cell Transplantation; D002478:Cells, Cultured; D005260:Female; D005315:Fetal Diseases; D017930:Genes, Reporter; D008297:Male; D018991:Myelin Proteolipid Protein / Q000172:deficiency / Q000235:genetics; D009186:Myelin Sheath / Q000235:genetics* / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology / Q000637:transplantation*; D020371:Pelizaeus-Merzbacher Disease / Q000196:embryology* / Q000235:genetics / Q000628:therapy*; D016548:Prosencephalon / Q000166:cytology; D051381:Rats; D011922:Rats, Mutant Strains; D013234:Stem Cells; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D018991:Myelin Proteolipid Protein; D001616:beta-Galactosidase