TMIC-34. INFILTRATIVE BEHAVIOR OF PATIENT-DERIVED GLIOBLASTOMA CELL LINES IN REGION-SPECIFIC HUMAN BRAIN ORGANOIDS

Abstract Glioblastoma (GBM) is the most common malignant brain tumor in adults. GBMs are known for their highly invasive and proliferative properties and are associated with a dismal prognosis (~12-18 months post-diagnosis). Neuroanatomical disparities in the occurrence of GBMs suggest that in addition to microenvironmental impacts, tumor cells are impacted by the cellular and molecular diversity across varying regions of this nervous system. This idea has been difficult to study due to the lack of human-specific models that effectively recapitulate the biological behaviors of GBMs in region-specific microenvironments. To address these challenges, we engrafted GFP-tagged patient-derived glioma cell lines into human induced pluripotent stem cell (hiPSC)-derived organoids patterned to mimic the most forebrain (dorsal cortex) and hindbrain (spinal cord) regions of the nervous system. Immunostaining assays at 2, 7, 14, and 21 days post-engraftment compared the extent of infiltration, as measured by the distance traveled by glioma cells, in both regions. We found that glioma cells infiltrated a significantly greater distance in the dorsal cortical organoids compared to the spinal cord organoids. This suggests a more conducive environment for glioma infiltration in the forebrain vs. hindbrain at baseline. We are currently determining if these regional biases in infiltration capacity are modified with either optogenetic stimulation of the host brain organoids or in the presence of interregional interactions in an assembloid system. Thus, using this fully human-specific platform, we aim to gain insights into the infiltrative behaviors of GBM cells, which will advance our understanding of this devastating disease.