Modeling Patient-Derived Glioblastoma with Cerebral Organoids

• Published in: Cell reports (Cambridge) 2019-03, Vol.26 (12), p.3203-3211.e5
• Main Authors: Linkous, Amanda, Balamatsias, Demosthenes, Snuderl, Matija, Edwards, Lincoln, Miyaguchi, Ken, Milner, Teresa, Reich, Batsheva, Cohen-Gould, Leona, Storaska, Andrew, Nakayama, Yasumi, Schenkein, Emily, Singhania, Richa, Cirigliano, Stefano, Magdeldin, Tarig, Lin, Ying, Nanjangud, Gouri, Chadalavada, Kalyani, Pisapia, David, Liston, Conor, Fine, Howard A.
• Format: Article
• Language: English
• Subjects: Brain Neoplasms - metabolism; Brain Neoplasms - pathology; brain tumors; cancer stem cells; cerebral organoids; glioblastoma; Glioblastoma - metabolism; Glioblastoma - pathology; glioma; glioma stem cells; human embryonic stem cells; Humans; Models, Biological; Neoplasm Invasiveness; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Organoids - metabolism; Organoids - pathology; stem-cell-based disease models; tissue engineering; tumor microtubes
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.02.063

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, we have established a model system whereby we can retro-engineer patient-specific GBMs using patient-derived glioma stem cells (GSCs) and human embryonic stem cell (hESC)-derived cerebral organoids. Our 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. Our GLICO model provides a system for modeling primary human GBM ex vivo and for high-throughput drug screening. [Display omitted] •Glioma stem cells home toward, invade, and proliferate in human cerebral organoids•GLICO (cerebral organoid glioma) tumors phenocopy patient glioblastoma•Tumor microtubes promote the invasion of GLICO tumors into normal host tissue•The GLICO model is a tool to study GBM biology in a human brain environment To address limitations with current preclinical glioblastoma (GBM) models, Linkous et al. establish a “GLICO” (cerebral organoid glioma) model to retro-engineer patient-specific GBMs using patient-derived glioma stem cells and human cerebral organoids. Resulting tumors closely phenocopy patient GBMs and are supported by tumor microtubes that promote invasion into host tissue.