Publication

Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology

Journal Paper/Review - Jun 27, 2019

Units
PubMed
Doi

Citation
Ravi V, Hofmann U, Schnell O, Beck J, Follo M, Delev D, Mader I, Shah M, Sankowski R, Meyer-Luehmann M, Franco P, Naseri Y, d'Errico P, Garrelfs N, Behringer S, Wurm J, Joseph K, Heiland D. Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology. Life Sci Alliance 2019; 2
Type
Journal Paper/Review (English)
Journal
Life Sci Alliance 2019; 2
Publication Date
Jun 27, 2019
Issn Electronic
2575-1077
Brief description/objective

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.