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

Life Sci Alliance. 2019 Jun 27;2(4):e201900305. doi: 10.26508/lsa.201900305. Print 2019 Aug.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Astrocytes / metabolism
  • Brain / cytology
  • Brain / metabolism
  • Brain / surgery
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / immunology
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / pathology
  • Cell Movement
  • Cell Proliferation
  • Female
  • Glioblastoma* / drug therapy
  • Glioblastoma* / immunology
  • Glioblastoma* / metabolism
  • Glioblastoma* / pathology
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Models, Biological
  • Nerve Tissue / cytology
  • Nerve Tissue / metabolism
  • Nerve Tissue / surgery
  • Temozolomide / pharmacology
  • Tissue Culture Techniques / methods*
  • Tumor Microenvironment

Substances

  • Temozolomide