Cancer survivors\u00a0frequently\u00a0experience long-term neurocognitive impairments following chemotherapy and cranial irradiation; however, clinically relevant experimental models that accurately recapitulate therapy-induced neurotoxicity are limited. In this study, we developed a human three-dimensional (3D) neural tissue model derived from L-MYC\u2013immortalized human neural stem cells (LMNSCs) to investigate mechanisms of chemotherapy- and radiation-induced brain injury and to evaluate extracellular vesicle (EV)\u2013mediated neuroprotection. LMNSC-derived\u00a0cells in\u00a03D\u00a0cultures\u00a0containing\u00a0neuronal, glial, and oligodendrocyte progenitor populations were exposed to methotrexate or ionizing radiation to model\u00a0cancer\u00a0treatment-associated neurotoxicity. Cellular injury and lineage-specific vulnerability were assessed using flow cytometry, transcriptomic profiling, and molecular analyses of neural and glial markers. Both treatments induced\u00a0significant damage\u00a0to neuronal and\u00a0oligodendroglial\u00a0populations and altered transcriptional programs associated with neuroinflammation, synaptic function, and cellular stress responses. Treatment with neural stem cell\u2013derived EVs promoted recovery of neural cell populations and partially restored transcriptional pathways involved in neuronal survival, neurogenesis, and tissue repair. These findings\u00a0demonstrate\u00a0that LMNSC-derived 3D neural tissue models provide a physiologically relevant platform for studying therapy-induced neurotoxicity and\u00a0identifying\u00a0regenerative interventions. Furthermore, our results support the potential of neural stem cell\u2013derived EVs as a cell-free therapeutic strategy to mitigate chemotherapy- and radiation-induced brain injury. This platform may\u00a0facilitate\u00a0mechanistic studies and accelerate the development of neuroprotective therapies for cancer survivors.<\/p>\n
Dr. Margarita Gutova is an Assistant Professor in the Department of Stem Cell Biology and Regenerative Medicine at City of Hope. She leads a translational research program focused on developing neural stem cell-based and extracellular vesicle-based therapies for neurological diseases and brain tumors. Her work integrates human neural stem cell platforms, patient-derived tumor models, and advanced 3D brain tissue systems to study mechanisms of neuroprotection, neurotoxicity, and tumor\u2013immune interactions. Dr. Gutova\u2019s research aims to advance precision regenerative medicine and immunotherapy approaches for glioblastoma and cancer treatment-related neurocognitive impairments.<\/p>\n","protected":false},"featured_media":5097,"template":"","meta":{"_acf_changed":false},"schedule":[5],"speaker-category":[6],"class_list":["post-5096","speaker","type-speaker","status-publish","has-post-thumbnail","hentry","schedule-day-1","speaker-category-speakers"],"acf":[],"yoast_head":"\n