title: Human embryonic stem cell-derived oligodendrocyte progenitors remyelinate the brain and rescue behavioral deficits following radiation.
abstract: Radiation therapy to the brain is a powerful tool in the management of many cancers, but it is associated with significant and irreversible long-term side effects, including cognitive decline and impairment of motor coordination. Depletion of oligodendrocyte progenitors and demyelination are major pathological features that are particularly pronounced in younger individuals and severely limit therapeutic options. Here we tested whether human ESC-derived oligodendrocytes can functionally remyelinate the irradiated brain using a rat model. We demonstrate the efficient derivation and prospective isolation of human oligodendrocyte progenitors, which, upon transplantation, migrate throughout the major white matter tracts resulting in both structural and functional repair. Behavioral testing showed complete recovery of cognitive function while additional recovery from motor deficits required concomitant transplantation into the cerebellum. The ability to repair radiation-induced damage to the brain could dramatically improve the outlook for cancer survivors and enable more effective use of radiation therapies, especially in children.
authors: Department of Neurosurgery and Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Jinghua
authors: J
authors: Piao
authors: Department of Neurosurgery and Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Tamara
authors: T
authors: Major
authors: Department of Neurosurgery and Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Gordon
authors: G
authors: Auyeung
authors: Department of Neurosurgery and Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Edelweiss
authors: E
authors: Policarpio
authors: Department of Neurosurgery and Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Jayanthi
authors: J
authors: Menon
authors: Department of Neurosurgery and Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Leif
authors: L
authors: Droms
authors: Department of Neurosurgery and Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Philip
authors: P
authors: Gutin
authors: Resource Center (EMRC), The Rockefeller University, New York, NY 10065, USA.
authors: Kunihiro
authors: K
authors: Uryu
authors: Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA.
authors: Jason
authors: J
authors: Tchieu
authors: Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, QC, Canada, G1V 0A6; Axe Neuroscience, Centre de recherche du CHU de Québec, QC, Canada, G1V 0A6.
authors: Denis
authors: D
authors: Soulet
authors: Department of Neurosurgery and Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. Electronic address: tabarv@mskcc.org.
authors: Viviane
authors: V
authors: Tabar
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000503:physiopathology / Q000528:radiation effects*; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology* / Q000637:transplantation; D051381:Rats; D011923:Rats, Nude; D014965:X-Rays