Strategies for developing complex multi-component in vitro tumor models: Highlights in glioblastoma.

Strategies for developing complex multi-component in vitro tumor models: Highlights in glioblastoma.
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DOI:
10.1016/j.addr.2021.114067
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发表时间:
2022-01
影响因子:
16.1
通讯作者:
--
中科院分区:
医学1区
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近年来,许多研究小组已经开始利用生物工程体外癌症模型来研究疾病进展的机制,测试候选药物,并开发平台以推进个性化药物治疗选择。由于过去几十年来细胞和组织工程的进步,现在有无数的工具可以用来创建这样的体外系统。在这篇综述中,我们描述了开发模型系统时必须考虑的因素,这些模型系统准确地模拟了体内肿瘤微环境(TME),并可用于回答特定的科学问题。我们将总结一种或多种细胞类型的模型中细胞来源的重要性,并概述选择准确模拟肿瘤或组织的天然细胞外基质(ECM)的生物材料的重要性。然后,我们提供了这两个组件如何在各种模型形状因子中协同使用的示例,并通过讨论生物打印和器官芯片制造等生物制造技术如何用于创建高度可重复的复杂体外模型来得出结论。由于该主题具有广泛的应用范围,我们利用评论的最后一部分更深入地探讨一种类型的癌症(胶质母细胞瘤),以说明这些成分如何结合在一起,以进一步加深我们对癌症生物学的了解,并使我们更接近开发新型癌症。改善患者预后的药物和系统。
In recent years, many research groups have begun to utilize bioengineered in vitro models of cancer to study mechanisms of disease progression, test drug candidates, and develop platforms to advance personalized drug treatment options. Due to advances in cell and tissue engineering over the last few decades, there are now a myriad of tools that can be used to create such in vitro systems. In this review, we describe the considerations one must take when developing model systems that accurately mimic the in vivo tumor microenvironment (TME) and can be used to answer specific scientific questions. We will summarize the importance of cell sourcing in models with one or multiple cell types and outline the importance of choosing biomaterials that accurately mimic the native extracellular matrix (ECM) of the tumor or tissue that is being modeled. We then provide examples of how these two components can be used in concert in a variety of model form factors and conclude by discussing how biofabrication techniques such as bioprinting and organ-on-a-chip fabrication can be used to create highly reproducible complex in vitro models. Since this topic has a broad range of applications, we use the final section of the review to dive deeper into one type of cancer, glioblastoma, to illustrate how these components come together to further our knowledge of cancer biology and move us closer to developing novel drugs and systems that improve patient outcomes.
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