三维培养模型在神经胶质瘤研究中的应用——当前趋势和未来展望。

Three-dimensional culture models to study glioblastoma - current trends and future perspectives.

机构信息

Department of Clinical Medicine, Aarhus University, Denmark.

Department of Biomedicine, Aarhus University, Denmark.

出版信息

Curr Opin Pharmacol. 2021 Dec;61:91-97. doi: 10.1016/j.coph.2021.08.019. Epub 2021 Oct 14.

Abstract

Glioblastoma (GBM) is the most prevalent form of primary malignant brain tumor in adults and remains almost invariably lethal owing to its aggressive and invasive nature. There have only been marginal improvements in its bleak survival rate of 12-15 months over the last four decades. The lack of preclinical models that efficiently recapitulate tumor biology and the tumor microenvironment is also in part responsible for the slow phase of translational GBM research. Emerging three-dimensional (3D) organoids and cell culture systems offer new and innovative possibilities for GBM modelling. These 3D models find their application to engineer the disease, screen drugs, establishing live biobank, and explore personalized therapy. Furthermore, these models can also be genetically modified by using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology, which would allow one to study the specific role of key genes associated with gliomagenesis. Establishment of a coculture system with GBM cells to understand its invasive behavior is yet another major application of this model. Despite these merits, the organoid models also have certain limitations, including the absence of immune responses and vascular systems. In recent years, major progress has been made in the development and refinement of 3D models of GBM. In this review, we intend to highlight these recent advances and the potential future implications of this rapidly evolving field, which should facilitate a better understanding of GBM biology.

摘要

胶质母细胞瘤(GBM)是成人中最常见的原发性恶性脑肿瘤,由于其侵袭性和浸润性,几乎总是致命的。在过去的四十年中,其生存率仅略有提高,仅为 12-15 个月。缺乏能够有效重现肿瘤生物学和肿瘤微环境的临床前模型也是导致胶质母细胞瘤转化研究进展缓慢的部分原因。新兴的三维(3D)类器官和细胞培养系统为胶质母细胞瘤建模提供了新的创新可能性。这些 3D 模型可用于工程疾病、筛选药物、建立活体生物库和探索个性化治疗。此外,这些模型还可以通过使用成簇规律间隔短回文重复序列(CRISPR)/Cas9 技术进行基因修饰,从而可以研究与胶质瘤发生相关的关键基因的特定作用。建立与 GBM 细胞共培养系统以了解其侵袭行为是该模型的另一个主要应用。尽管具有这些优点,但类器官模型也存在某些局限性,包括缺乏免疫反应和血管系统。近年来,GBM 3D 模型的开发和改进取得了重大进展。在这篇综述中,我们旨在强调这些最新进展以及该快速发展领域的潜在未来意义,这将有助于更好地了解 GBM 生物学。

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