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病人来源胶质母细胞瘤类器官体可涵盖肿瘤异质性
作者:小柯机器人 发布时间:2019/12/27 15:22:01

美国宾夕法尼亚大学Hongjun Song、Guo-li Ming、Donald M. O’Rourke等研究人员合作建立了病人来源的胶质母细胞瘤类器官体模型和生物库,其能够涵盖了肿瘤间和肿瘤内的异质性。相关论文于2019年12月26日在线发表在《细胞》杂志上。

研究人员报告了用于产生和保存患者来源胶质母细胞瘤类器官体(GBO)的方法,这些类器官体涵盖了其相应亲本肿瘤的组织学特征、细胞多样性、基因表达和突变特征。GBO能够高度可靠地快速产生,并且在移植到成年啮齿动物大脑中后会表现出快速的侵袭性。

研究人员进一步证明了GBO测试个性化疗法的实用性,即检测GBO突变谱与对特定药物的反应以及对嵌合抗原受体T细胞免疫疗法的建模。这项研究表明,GBO保留了胶质母细胞瘤的许多关键特征,可以迅速用于研究针对患者的治疗策略。此外,研究人员建立的生物库为基础的和转化的胶质母细胞瘤研究提供了丰富的资源。

研究人员表示,胶质母细胞瘤表现出巨大的肿瘤间和肿瘤内的异质性,使有效治疗策略的研发变得复杂。目前的体外模型在保留亲本肿瘤的细胞和突变多样性方面受到限制,并且需要更长的产生时间。

附:英文原文

Title: A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity

Author: Fadi Jacob, Ryan D. Salinas, Daniel Y. Zhang, Phuong T.T. Nguyen, Jordan G. Schnoll, Samuel Zheng Hao Wong, Radhika Thokala, Saad Sheikh, Deeksha Saxena, Stefan Prokop, Di-ao Liu, Xuyu Qian, Dmitriy Petrov, Timothy Lucas, H. Isaac Chen, Jay F. Dorsey, Kimberly M. Christian, Zev A. Binder, MacLean Nasrallah, Steven Brem, Donald M. O’Rourke, Guo-li Ming, Hongjun Song

Issue&Volume: December 26, 2019

Abstract: Glioblastomas exhibit vast inter- and intra-tumoral heterogeneity, complicating the development of effective therapeutic strategies. Current in vitro models are limited in preserving the cellular and mutational diversity of parental tumors and require a prolonged generation time. Here, we report methods for generating and biobanking patient-derived glioblastoma organoids (GBOs) that recapitulate the histological features, cellular diversity, gene expression, and mutational profiles of their corresponding parental tumors. GBOs can be generated quickly with high reliability and exhibit rapid, aggressive infiltration when transplanted into adult rodent brains. We further demonstrate the utility of GBOs to test personalized therapies by correlating GBO mutational profiles with responses to specific drugs and by modeling chimeric antigen receptor T cell immunotherapy. Our studies show that GBOs maintain many key features of glioblastomas and can be rapidly deployed to investigate patient-specific treatment strategies. Additionally, our live biobank establishes a rich resource for basic and translational glioblastoma research.

DOI: 10.1016/j.cell.2019.11.036

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31321-2

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/