Paolillo Mayra, Comincini Sergio, Schinelli Sergio
Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy.
Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy.
Cancers (Basel). 2021 May 18;13(10):2449. doi: 10.3390/cancers13102449.
Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, with an average survival time of about one year from initial diagnosis. In the attempt to overcome the complexity and drawbacks associated with in vivo GBM models, together with the need of developing systems dedicated to screen new potential drugs, considerable efforts have been devoted to the implementation of reliable and affordable in vitro GBM models. Recent findings on GBM molecular features, revealing a high heterogeneity between GBM cells and also between other non-tumor cells belonging to the tumoral niche, have stressed the limitations of the classical 2D cell culture systems. Recently, several novel and innovative 3D cell cultures models for GBM have been proposed and implemented. In this review, we first describe the different populations and their functional role of GBM and niche non-tumor cells that could be used in 3D models. An overview of the current available 3D in vitro systems for modeling GBM, together with their major weaknesses and strengths, is presented. Lastly, we discuss the impact of groundbreaking technologies, such as bioprinting and multi-omics single cell analysis, on the future implementation of 3D in vitro GBM models.
多形性胶质母细胞瘤（GBM）是成人中最致命的原发性脑肿瘤，从初次诊断起平均生存时间约为一年。为了克服与体内GBM模型相关的复杂性和缺点，同时满足开发用于筛选新的潜在药物的系统的需求，人们致力于建立可靠且经济实惠的体外GBM模型。关于GBM分子特征的最新研究结果表明，GBM细胞之间以及属于肿瘤微环境的其他非肿瘤细胞之间存在高度异质性，这凸显了经典二维细胞培养系统的局限性。最近，已经提出并实施了几种用于GBM的新颖创新的三维细胞培养模型。在这篇综述中，我们首先描述了可用于三维模型的GBM和微环境非肿瘤细胞的不同群体及其功能作用。本文概述了当前用于模拟GBM的三维体外系统，以及它们的主要弱点和优势。最后，我们讨论了生物打印和多组学单细胞分析等突破性技术对三维体外GBM模型未来应用的影响。
