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Modeling Patient-Derived Glioblastoma with Cerebral Organoids.

TitleModeling Patient-Derived Glioblastoma with Cerebral Organoids.
Publication TypeJournal Article
Year of Publication2019
AuthorsLinkous 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 HA
JournalCell Rep
Volume26
Issue12
Pagination3203-3211.e5
Date Published2019 03 19
ISSN2211-1247
KeywordsBrain Neoplasms, Glioblastoma, Humans, Models, Biological, Neoplasm Invasiveness, 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.

DOI10.1016/j.celrep.2019.02.063
Alternate JournalCell Rep
PubMed ID30893594
PubMed Central IDPMC6625753
Grant ListDP1 CA228040 / CA / NCI NIH HHS / United States

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