Stem cell-derived extracellular vesicles to reverse radiation-induced brain injury

This study determined the neuroprotective ability of human neural stem cell (hNSC)-derived exosomes in brain cancer-bearing mice exposed to irradiation and chemotherapy. Using a mouse model of brain cancer, our preclinical studies found that hNSC-derived, nanoscale, extracellular vesicles (EVs) alleviate the adverse effects of brain cancer therapy on cognitive function. Multiple doses of brain radiation therapy (RT) in combination with temozolomide chemotherapy (TMZ) is a standard of care for the treatment of brain cancers. RT-TMZ can reduce cancer growth. However, it often leads to cognitive function decline in cancer survivors. We found that intravenous injection of stem cell-derived EVs reduced cognitive decline in brain cancer-bearing mice exposed to RT-TMZ. Stem cell EV also effectively reduced inflammation in the brain and prevented the loss of synaptic proteins, the memory-forming units in the brain. Stem cell-derived EVs neither interfere with the cancer-killing ability of RT-TMZ treatment nor induce any toxicity in vital organs. Stem cell-derived EVs minimize the risk of immunorejection, inflammation, or teratoma formation, thus obviating the need for extensive immunosuppression. This strategy has high translational potential to mitigate brain cancer therapy-induced cognitive impairments.