Human embryonic stem cell-derived oligodendrocyte progenitors remyelinate the brain and rescue behavioral deficits following radiation Journal Article

Authors: Piao, J.; Major, T.; Auyeung, G.; Policarpio, E.; Menon, J.; Droms, L.; Gutin, P.; Uryu, K.; Tchieu, J.; Soulet, D.; Tabar, V.
Article 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. © 2015 Elsevier Inc.
Keywords: immunohistochemistry; controlled study; nonhuman; brain radiation; myelin basic protein; cerebellum; platelet derived growth factor alpha receptor; oligodendrocyte transcription factor 2; animal experiment; brain cortex; stem cell transplantation; radiation injury; cancer survivor; stem cell; nerve cell adhesion molecule; rat; cognition; rattus; myelin; myelination; corpus callosum; oligodendroglia; demyelination; transcription factor nkx2.2; myelin associated glycoprotein; transcription factor sox10; priority journal; article; claudin 11; embryonic stem cell derived oligodendrocyte; embryonic stem cell derived oligodendrocyte transplantation; hippocampal fimbria
Journal Title: Cell Stem Cell
Volume: 16
Issue: 2
ISSN: 1934-5909
Publisher: Cell Press  
Date Published: 2015-02-05
Start Page: 198
End Page: 210
Language: English
DOI: 10.1016/j.stem.2015.01.004
PROVIDER: scopus
PUBMED: 25658373
PMCID: PMC4425211
Notes: Export Date: 2 April 2015 -- Source: Scopus
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MSK Authors
  1. Viviane S Tabar
    120 Tabar
  2. Philip H Gutin
    152 Gutin
  3. Tamara Major
    4 Major
  4. Jinghua Piao
    5 Piao
  5. Jayanthi Menon
    7 Menon
  6. Jason Hung Tchieu
    11 Tchieu
  7. Leif Asher Droms
    5 Droms