Establishment of patient-derived organoid models of lower-grade glioma.
Establishment of patient-derived organoid models of lower-grade glioma.
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建立低级神经胶质瘤的患者衍生的器官模型。
DOI：
10.1093/neuonc/noab273
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发表时间：
2022-04-01
期刊：
影响因子：
15.9
通讯作者：
McBrayer SK
中科院分区：
文献类型：
--
作者：
Abdullah KG;Bird CE;Buehler JD;Gattie LC;Savani MR;Sternisha AC;Xiao Y;Levitt MM;Hicks WH;Li W;Ramirez DMO;Patel T;Garzon-Muvdi T;Barnett S;Zhang G;Ashley DM;Hatanpaa KJ;Richardson TE;McBrayer SK
从历史上看，创建低级别胶质瘤（LGG）的患者衍生模型一直具有挑战性，导致支持这种疾病的实验室研究的实验平台很少。虽然类器官建模方法最近已被用于创建高级别胶质瘤（HGG）的体外模型，但尚不清楚这种方法是否可以成功应用于LGG。在这项研究中，我们开发了一种优化的方案，通过利用生理（5%）氧合条件从LGG原代组织样品中建立类器官，并利用它来产生第一个已知的这些模型。为了评估它们的保真度，我们使用代谢、基因组、组织学和谱系标志物基因表达测定来调查患者来源的类器官的关键生物学特征。从胶质瘤组织学亚型和肿瘤等级（WHO 1-4级）的原发性肿瘤样本中创建类器官模型的成功率为91%（n = 20/22），WHO 1-3级肿瘤的成功率为87%（13/15）。患者来源的类器官概括了其各自亲代肿瘤标本的干性、增殖性和肿瘤间质组成特征。亲代肿瘤的细胞结构、突变和代谢特征也是保守的。重要的是，LGG类器官在体外维持数周至数月，并在生物库后恢复活力，而不丧失完整性。我们报告了一种有效的方法，生产忠实的体外模型LGG。通过这种方法产生的新的实验平台很好地定位于支持这种疾病的临床前研究，特别是与肿瘤免疫学，肿瘤-基质相互作用，新药物靶点的鉴定和治疗反应谱的个性化评估相关的研究。
Historically, creating patient-derived models of lower-grade glioma (LGG) has been challenging, contributing to few experimental platforms that support laboratory-based investigations of this disease. Although organoid modeling approaches have recently been employed to create in vitro models of high-grade glioma (HGG), it is unknown whether this approach can be successfully applied to LGG. In this study, we developed an optimized protocol for the establishment of organoids from LGG primary tissue samples by utilizing physiologic (5%) oxygenation conditions and employed it to produce the first known suite of these models. To assess their fidelity, we surveyed key biological features of patient-derived organoids using metabolic, genomic, histologic, and lineage marker gene expression assays. Organoid models were created with a success rate of 91% (n = 20/22) from primary tumor samples across glioma histological subtypes and tumor grades (WHO Grades 1–4), and a success rate of 87% (13/15) for WHO Grade 1–3 tumors. Patient-derived organoids recapitulated stemness, proliferative, and tumor-stromal composition profiles of their respective parental tumor specimens. Cytoarchitectural, mutational, and metabolic traits of parental tumors were also conserved. Importantly, LGG organoids were maintained in vitro for weeks to months and reanimated after biobanking without loss of integrity. We report an efficient method for producing faithful in vitro models of LGG. New experimental platforms generated through this approach are well positioned to support preclinical studies of this disease, particularly those related to tumor immunology, tumor-stroma interactions, identification of novel drug targets, and personalized assessments of treatment response profiles.
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影响因子：
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作者：
Pernik MN;Bird CE;Traylor JI;Shi DD;Richardson TE;McBrayer SK;Abdullah KG
通讯作者：
Abdullah KG
DOI：
10.4161/cc.8.20.9701
发表时间：
2009-10-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Heddleston JM;Li Z;McLendon RE;Hjelmeland AB;Rich JN
通讯作者：
Rich JN
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
50.3
作者：
Blouw, B;Song, HQ;Bergers, G
通讯作者：
Bergers, G
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW