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Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology.
Life Science Alliance ( IF 3.3 ) Pub Date : 2019-06-27 , DOI: 10.26508/lsa.201900305
Vidhya M Ravi 1, 2, 3, 4 , Kevin Joseph 3, 4, 5 , Julian Wurm 4, 5 , Simon Behringer 4, 5 , Nicklas Garrelfs 4, 5 , Paolo d'Errico 4, 6 , Yashar Naseri 3, 4 , Pamela Franco 3, 4 , Melanie Meyer-Luehmann 4, 6 , Roman Sankowski 4, 7 , Mukesch Johannes Shah 3, 4 , Irina Mader 8 , Daniel Delev 9 , Marie Follo 4, 10 , Jürgen Beck 3, 4 , Oliver Schnell 3, 4, 5 , Ulrich G Hofmann 2, 3, 4 , Dieter Henrik Heiland 1, 3, 4
Affiliation  

When it comes to the human brain, models that closely mimic in vivo conditions are lacking. Living neuronal tissue is the closest representation of the in vivo human brain outside of a living person. Here, we present a method that can be used to maintain therapeutically resected healthy neuronal tissue for prolonged periods without any discernible changes in tissue vitality, evidenced by immunohistochemistry, genetic expression, and electrophysiology. This method was then used to assess glioblastoma (GBM) progression in its natural environment by microinjection of patient-derived tumor cells into cultured sections. The result closely resembles the pattern of de novo tumor growth and invasion, drug therapy response, and cytokine environment. Reactive transformation of astrocytes, as an example of the cellular nonmalignant tumor environment, can be accurately simulated with transcriptional differences similar to those of astrocytes isolated from acute GBM specimens. In a nutshell, we present a simple method to study GBM in its physiological environment, from which valuable insights can be gained. This technique can lead to further advancements in neuroscience, neuro-oncology, and pharmacotherapy.

中文翻译:

人类器官型脑片培养:神经肿瘤环境研究的新框架。

当涉及到人类的大脑时,缺少能够模仿体内条件的模型。活的神经元组织是活人之外体内人脑的最接近表示。在这里,我们提出了一种方法,可用于长期维持经治疗切除的健康神经元组织,而无需通过免疫组织化学,基因表达和电生理学证明组织活力发生任何明显变化。然后,通过将患者来源的肿瘤细胞显微注射到培养的切片中,将该方法用于评估其自然环境中的胶质母细胞瘤(GBM)进展。结果与从头肿瘤生长和侵袭,药物治疗反应以及细胞因子环境的模式非常相似。星形胶质细胞的反应性转化,例如细胞非恶性肿瘤环境,可以用类似于从急性GBM标本中分离出的星形胶质细胞的转录差异精确模拟。简而言之,我们提出了一种在其生理环境中研究GBM的简单方法,可以从中获得有价值的见解。这种技术可以导致神经科学,神经肿瘤学和药物治疗方面的进一步发展。
更新日期:2020-08-21
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