脑胶质母细胞瘤模型研究概况及类脑模型的研发应用

doi:10.6040/j.issn.1671-7554.0.2020.0601

山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (8): 74-80.doi: 10.6040/j.issn.1671-7554.0.2020.0601

• 脑科学与类脑智能研究专题 • 上一篇下一篇

脑胶质母细胞瘤模型研究概况及类脑模型的研发应用

王剑^1,^2,^3,*(),周文婧^1,²,薛知易^1,²,刘晓菲^1,²

1. 山东大学齐鲁医院神经外科，山东大学脑与类脑科学研究院, 山东济南 250012
2. 山东省脑功能重构重点实验室, 山东济南 250012
3. 挪威卑尔根大学生物医学系, 西部郡卑尔根 5009

收稿日期:2020-04-15 出版日期:2020-08-01 发布日期:2020-08-07
通讯作者: 王剑 E-mail:jian.wang@sdu.edu.cn
作者简介:王剑，教授，博士研究生导师，泰山学者特聘专家，挪威卑尔根大学教授、博士研究生导师。现任山东大学脑与类脑科学研究院常务副院长、山东大学脑科学研究所常务副所长、中国-挪威脑科学研究中心常务副主任。兼任山东大学国际合作联络教授、中国医师协会脑胶质瘤专委会基础研究与转化专委会委员、中国研究型医院脑功能研究与转化专业委员会常委、美国癌症研究协会和国际干细胞研究学会会员。主持国家自然科学基金面上项目、山东省重大科技创新工程项目、山东省自然科学基金等课题及挪威卑尔根大学及政府多项科研项目。在《EMBO Molecular Medicine》《Brain》、《Autophagy》《Clinical Cancer Research》《Oncogene》等期刊发表SCI论文70余篇，培养博士和硕士研究生20余名。先后受邀在美国、法国、韩国、日本等多个国家举办的国际性大会上做学术报告
基金资助:
国家自然科学基金面上项目(81972351);山东省重大科技创新工程项目(2017CXGC1502);山东省自然科学基金面上项目(ZR2017MH116);山东省泰山学者基金(tshw201502056)

Overview of glioblastoma models and development and application of brain organoids

Jian WANG^1,^2,^3,*(),Wenjing ZHOU^1,²,Zhiyi XUE^1,²,Xiaofei LIU^1,²

1. Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, Shandong, China
2. Shandong Key Laboratory of Brain Function Remodeling, Jinan 250012, Shandong, China
3. Department of Biomedicine, University of Bergen, Bergen 5009, Vestland, Norway

Received:2020-04-15 Online:2020-08-01 Published:2020-08-07
Contact: Jian WANG E-mail:jian.wang@sdu.edu.cn

摘要/Abstract

摘要：

胶质母细胞瘤是恶性程度最高的胶质瘤，建立针对胶质母细胞瘤弥漫性、浸润性生长特征的实验模型，是基础研究的核心。本文系统梳理了近年来国内外有关脑胶质母细胞瘤体内和体外研究模型的建立方法、应用概况及局限性，指出现有的脑胶质母细胞瘤研究模型虽在不断改进与完善，且在某些方面推进了该病的基础研究，但却无法模拟人体脑胶质母细胞瘤生长的复杂环境，揭示该病的动态发病机制及可能的药物作用途径。课题组经过多年的探索，研发了类脑器官模型，该模型可模拟大鼠体内大脑的发育过程，并与颅脑胶质母细胞瘤模型建立了共培养系统，能实现体外直观的实时观察肿瘤细胞的侵袭特征，为进一步研究脑胶质母细胞瘤的发病机制奠定了基础。并可从中分选出侵袭性肿瘤细胞与非侵袭性肿瘤细胞，进行下一步基因组学的系统分析，从而有望筛选出靶向侵袭性胶质母细胞瘤细胞的药物。

关键词: 胶质母细胞瘤, 离体模型, 类脑器官, 类肿瘤球, 共培养

Abstract:

Glioblastoma (GBM) is the most common primary brain tumor with high morbidity and high mortality. The primary goal of researches on GBM is to establish models to recapitulate the tumor invasive phenotype. In this review, we have systematically summarized the in vitro and in vivo models in GBM study by discussing the establishment and applications as well as their limitations. We acknowledge the development of various model systems in recent years which has substantially improved GBM research activities. However, largely due to difficulties of recapitulating the complicated microenvironment in GBM, it remains challenging to explore the tumor developmental mechanism and candidate drug efficacy in the treatment. Our team has extensively studied GBM for many years and established an ex-vivo model using rat brain organoids. Extensive data show that the model can highly mimic the process of brain development. Together with GBM patient-derived tumor spheroids and brain organoids, we have established co-culture model systems in order to in real time study the invasive GBM, which may fundamentally help us to understand the tumor development. Moreover, using the system, we are able to sort the invasive tumor cells from non-invasive tumor cells and analyze single cell RNA sequences to identify key molecules, which will be possible in turn to offer us new therapeutic candidates potentially targeting GBM.

Key words: Glioblastoma, Ex-vivo model, Brain organoid, Tumor spheroid, Co-culture

中图分类号:

R739.4

王剑,周文婧,薛知易,刘晓菲. 脑胶质母细胞瘤模型研究概况及类脑模型的研发应用[J]. 山东大学学报 (医学版), 2020, 58(8): 74-80.

Jian WANG,Wenjing ZHOU,Zhiyi XUE,Xiaofei LIU. Overview of glioblastoma models and development and application of brain organoids[J]. Journal of Shandong University (Health Sciences), 2020, 58(8): 74-80.

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脑胶质母细胞瘤模型研究概况及类脑模型的研发应用

Overview of glioblastoma models and development and application of brain organoids

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