Implementing neuroprotective strategies for resolving normal tissue toxicities in the brain: From stem cells to electrons

Cancer treatments involving ionizing radiation and/or chemotherapeutics frequently result in progressive and debilitating cognitive dysfunction that severely compromises quality of life, a problem of particular concern to pediatric cancer survivors.  Despite the prevalence of this problem and the growing recognition that neurocognitive health represents a critical criterion for evaluating therapeutic outcome, strategies aimed at ameliorating cognitive decline have been hampered by the lack of long-term satisfactory solutions.

To address this unmet medical need, we have developed preclinical models involving the intrahippocampal transplantation of human stem cells and/or the systemic injection of stem cell-derived extracellular vesicles.  Significant data has now shown that this approach can ameliorate the adverse effects of radiation and chemotherapy on the brain. 

Stem cells and extracellular vesicles resolve cognitive deficits over extended post-treatment times as assessed through a battery of behavioral tasks, and exert their beneficial effects through the preservation of host neuronal morphology and the attenuation of neuroinflammation.  Additional and very recent data has also shown that similar protective mechanisms can be engaged by electron beams delivered at ultra-high (FLASH) dose rates.

This talk will highlight these recent and innovative advances in resolving neurocognitive complications associated with the treatment of primary and secondary CNS malignancies.