Steindl Ariane, Valiente Manuel
Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Brain Metastasis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Neuro Oncol. 2025 Feb 10;27(2):338-351. doi: 10.1093/neuonc/noae195.
Over recent decades, in vitro and in vivo models have significantly advanced brain cancer research; however, each presents distinct challenges for accurately mimicking in situ conditions. In response, organotypic slice cultures have emerged as a promising model recapitulating precisely specific in vivo phenotypes through an ex vivo approach. Ex vivo organotypic brain slice models can integrate biological relevance and patient-specific variability early in drug discovery, thereby aiming for more precise treatment stratification. However, the challenges of obtaining representative fresh brain tissue, ensuring reproducibility, and maintaining essential central nervous system (CNS)-specific conditions reflecting the in situ situation over time have limited the direct application of ex vivo organotypic slice cultures in robust clinical trials. In this review, we explore the benefits and possible limitations of ex vivo organotypic brain slice cultures in neuro-oncological research. Additionally, we share insights from clinical experts in neuro-oncology on how to overcome these current limitations and improve the practical application of organotypic brain slice cultures beyond academic research.
在最近几十年里,体外和体内模型极大地推动了脑癌研究;然而,每种模型在精确模拟原位条件方面都面临着独特的挑战。作为回应,器官型切片培养作为一种有前景的模型应运而生,它通过一种离体方法精确地重现特定的体内表型。离体器官型脑切片模型能够在药物研发早期整合生物学相关性和患者特异性变异性,从而实现更精确的治疗分层。然而,获取具有代表性的新鲜脑组织、确保可重复性以及随时间维持反映原位情况的基本中枢神经系统(CNS)特定条件等挑战,限制了离体器官型切片培养在稳健的临床试验中的直接应用。在这篇综述中,我们探讨了离体器官型脑切片培养在神经肿瘤学研究中的益处和可能存在的局限性。此外,我们分享了神经肿瘤学临床专家关于如何克服当前这些局限性以及在学术研究之外改善器官型脑切片培养实际应用的见解。