Cerebral Organoids as a 3D Model for Glioma

The prognosis of patients with glioblastoma (GBM) remains dismal with a median survival of approximately 15 months. Current preclinical GBM models are limited by the lack of a “normal” human microenvironment and the inability of many tumor cell lines to accurately reproduce GBM biology. To address these limitations, our guest presenter and her team have established a unique model system whereby they can retro-engineer patient-specific GBMs using patient-derived glioma stem cells (GSCs) and human embryonic stem cell (hESC)-derived cerebral organoids. Their cerebral organoid glioma (GLICO) model shows that GSCs home toward the human cerebral organoid, and deeply invade and proliferate within the host tissue forming tumors that closely phenocopy patient GBMs. Furthermore, cerebral organoid tumors form rapidly and are supported by an interconnected network of tumor microtubes that aids in the invasion of normal host tissue. This GLICO model provides a new system for modeling primary human GBM ex vivo and for high throughput drug screening. Guest Presenter Bio: Dr. Amanda Linkous previously served as the Director of the Starr Foundation Cerebral Organoid Translational Core at Weill Cornell Medicine (New York, NY). She completed her postdoctoral training in the Neuro-Oncology Branch at the National Cancer Institute (Bethesda, MD). Dr. Linkous is currently the Scientific Center Manager for the NCI's Center for Systems Biology of Small Cell Lung Cancer (SCLC) at Vanderbilt University, where she is developing similar 3D model systems to study the biology and refractory nature of SCLC (Nashville, TN)