Extracellular Vesicles Derived from L-MYC Neural Stem Cells Mediate Neuroprotection in 3D Models of Chemotherapy- and Radiation-Induced Neurotoxicity
Background/Objectives: Cancer survivors frequently experience long-term neurocognitive impairments following chemotherapy and cranial irradiation, yet experimental models that enable mechanistic investigation of therapy-induced neurotoxicity at the transcriptional level remain limited. This study aimed to develop a human three-dimensional (3D) neural tissue model derived from L-Myc immortalized…
A groundbreaking study has revealed that extracellular vesicles derived from L-Myc neural stem cells (LMNSCs) can effectively counteract neurotoxicity induced by chemotherapy and radiation in a human 3D neural tissue model. Researchers created a 3D neural tissue using LMNSCs, which consisted of neurons, astrocytes, and oligodendrocytes. When exposed to methotrexate (MTX) or ionizing radiation, the cultures displayed dose-dependent injury, marked by a decline in neuronal complexity and glial populations.
Treatments with LMNSC-derived extracellular vesicles (EVs) led to the restoration of neuronal and glial populations in the injured tissues. Transcriptomic profiling of the irradiated cultures unveiled the activation of inflammation, DNA damage, and stress-response pathways, which were subsequently dampened following treatment with LMNSC-EVs.
This research paves the way for a human-relevant platform to study cancer therapy-induced neurotoxicity. Moreover, it highlights the potential of LMNSC-derived EVs as a safe, cell-free regenerative therapy that can restore the detrimental transcriptional programs linked to radiation-induced neural injury.
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