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Modeling Patient-Derived Glioblastoma with Cerebral Organoids.
Cell Reports ( IF 7.5 ) Pub Date : 2019-03-19 , DOI: 10.1016/j.celrep.2019.02.063
Amanda Linkous 1 , Demosthenes Balamatsias 1 , Matija Snuderl 2 , Lincoln Edwards 1 , Ken Miyaguchi 1 , Teresa Milner 3 , Batsheva Reich 3 , Leona Cohen-Gould 4 , Andrew Storaska 1 , Yasumi Nakayama 1 , Emily Schenkein 1 , Richa Singhania 1 , Stefano Cirigliano 1 , Tarig Magdeldin 1 , Ying Lin 1 , Gouri Nanjangud 5 , Kalyani Chadalavada 5 , David Pisapia 6 , Conor Liston 3 , Howard A Fine 7
Affiliation  

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.

中文翻译:

用脑类器官对患者来源的胶质母细胞瘤进行建模。

胶质母细胞瘤 (GBM) 患者的预后仍然不佳,中位生存期约为 15 个月。目前的临床前 GBM 模型受到缺乏“正常”人类微环境和许多肿瘤细胞系无法准确再现 GBM 生物学的限制。为了解决这些限制,我们建立了一个模型系统,我们可以使用来自患者的神经胶质瘤干细胞 (GSC) 和人类胚胎干细胞 (hESC) 衍生的脑类器官对患者特异性 GBM 进行逆向工程。我们的脑类器官神经胶质瘤 (GLICO) 模型显示,GSCs 归巢于人类大脑类器官,并在宿主组织内深度侵入和增殖,形成与患者 GBM 密切表型的肿瘤。此外,脑类器官肿瘤形成迅速,并由有助于侵入正常宿主组织的相互连接的肿瘤微管网络支持。我们的 GLICO 模型提供了一个用于离体模拟原代人类 GBM 和用于高通量药物筛选的系统。
更新日期:2019-03-20
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