Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Division of Pediatric Neurosurgery, Riley Hospital for Children, Indianapolis, IN, USA.
BMC Cancer. 2024 Nov 28;24(1):1465. doi: 10.1186/s12885-024-13187-5.
Pre-clinical animal models of human brain tumors have been invaluable tools for studying cancer pathogenesis and exploring novel treatment modalities. Such models recapitulate important aspects of the human disease such as the stem-progenitor-differentiated cell hierarchy. Although powerful, we argue that animal models are inherently limited in their ability to phenocopy certain important aspects of human brain tumor biology. We specifically highlight the inability of mouse models to generate certain forms aggressive pediatric medulloblastoma likely owing to cellular, anatomic, and genetic differences between the human and mouse brains. Additionally, we review some limitations of human brain tumor derived cell lines and outline why they are a sub-optimal system for purposes of pre-clinical modeling. Below, we present the case for human stem cell-based models of brain tumors, focusing mainly on glioblastoma and medulloblastoma. Drawing on several recently published studies, we review the exciting progress that has been made towards modeling human brain tumors using two-dimensional adherent stem cell cultures and three-dimensional organoids. We identify the important advances arrived at using these human stem cell-based models and suggest opportunities for future work in this direction. In this review article, we aim to highlight the utility and promises of human stem cell-based models of brain tumors as a complementary system to traditional transgenic animal and cell line systems.
人类脑肿瘤的临床前动物模型一直是研究癌症发病机制和探索新治疗方法的宝贵工具。这些模型再现了人类疾病的重要方面，如干细胞-祖细胞-分化细胞层次结构。尽管功能强大，但我们认为动物模型在模拟人类脑肿瘤生物学某些重要方面的能力上存在固有局限性。我们特别强调了由于人类和小鼠大脑之间的细胞、解剖和遗传差异，小鼠模型无法产生某些形式的侵袭性小儿髓母细胞瘤。此外，我们回顾了一些源于人类脑肿瘤的细胞系的局限性，并概述了它们为什么不是用于临床前建模的次优系统。在下面，我们提出了基于人类干细胞的脑肿瘤模型的案例，主要关注神经胶质瘤和髓母细胞瘤。借鉴最近发表的几项研究，我们回顾了使用二维贴壁干细胞培养物和三维类器官对人类脑肿瘤进行建模所取得的令人兴奋的进展。我们确定了使用这些基于人类干细胞的模型所取得的重要进展，并提出了在这一方向开展未来工作的机会。在这篇综述文章中，我们旨在强调基于人类干细胞的脑肿瘤模型作为传统转基因动物和细胞系系统的补充系统的实用性和潜力。
