Cell Stem Cell
Volume 16, Issue 2, 5 February 2015, Pages 198-210
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Clinical Progress
Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitors Remyelinate the Brain and Rescue Behavioral Deficits following Radiation

https://doi.org/10.1016/j.stem.2015.01.004Get rights and content
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Highlights

  • A clinical dose of brain radiation induces demyelination and behavioral deficits

  • Oligodendrocyte progenitors (hOPC) are derived from human pluripotent stem cells

  • hOPCs grafted in the forebrain remyelinate the brain and rescue cognitive deficits

  • hOPC grafts in the cerebellum are required for improvement in motor tasks

Summary

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.

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