Publication Type Academic Article
Authors Linkous A, Balamatsias D, Snuderl M, Edwards L, Miyaguchi K, Milner T, Reich B, Cohen-Gould L, Storaska A, Nakayama Y, Schenkein E, Singhania R, Cirigliano S, Magdeldin T, Lin Y, Nanjangud G, Chadalavada K, Pisapia D, Liston C, Fine H
Journal Cell Rep
Volume 26
Issue 12
Pagination 3203-3211.e5
Date Published 03/19/2019
ISSN 2211-1247
Keywords Brain Neoplasms, Glioblastoma, Models, Biological, Neoplastic Stem Cells, Organoids
Abstract 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.
DOI 10.1016/j.celrep.2019.02.063
PubMed ID 30893594
PubMed Central ID PMC6625753
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