Editors' ChoiceCancer

Oligodendrocyte precursors to the rescue

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Science Translational Medicine  18 Feb 2015:
Vol. 7, Issue 275, pp. 275ec30
DOI: 10.1126/scitranslmed.aaa8318

The treatment of tumors within the central nervous system presents challenges due to their anatomical location, and radiation remains the therapeutic mainstay. While effective, radiation induces long-term damage and impacts memory formation and storage, which means that its use has to be limited particularly in pediatric cases. Through the transplantation of oligodendrocyte precursor cells derived from human embryonic stem cells, Piao et al. demonstrate that the learning and memory defects induced by radiation can be attenuated in rats.

The use of cranial radiotherapy has been hampered by the cognitive defects it induces, which are a result of cellular changes including reduced progenitor cell populations that lead to altered neurogenesis and white matter repair. In a rat model, the authors show that oligodendrocyte precursor cells and myelin are reduced after cranial radiotherapy. Using well-established protocols to generate oligodendrocyte precursor cells from human embryonic stem cells, the authors show that these cells can myelinate neurons in vitro in co-culture. When transplanted into irradiated rat brains, the human oligodendrocyte precursor cells myelinated neurons and replenished damaged white matter. When human oligodendrocyte precursor cells were transplanted into the rat cortex, the cognitive deficits induced by radiation were abrogated. Motor coordination could also be rescued when human oligodendrocyte precursor cells were transplanted into the rat cerebellum, demonstrating that the regenerative capacity of this approach was not limited to one region of the brain. Importantly, the transplanted cells were not tumorigenic, which is an important consideration for the clinical translation of this strategy.

As transplantation of stem and precursor cell populations are being evaluated for treating a variety of diseases, their use in reducing the side effects of radiation may be another important application. Follow-up studies interrogating the timing of transplantation and oligodendrocyte precursor cell use in pre-clinical brain tumor models will help to establish the efficacy of this approach and pave the way for the clinical evaluation of this cell therapy after cranial irradiation.

J. Piao et al., Human embryonic stem cell-derived oligodendrocyte progenitor cells remyelinate the brain and rescue behavioral deficits following radiation. Cell Stem Cell 10.1016/j.stem.2015.01.004 (2015).[Abstract]

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