3D-Bioprinted Mini-Brain: A Glioblastoma Model to Study Cellular Interactions and Therapeutics

Adv Mater. 2019 Apr;31(14):e1806590. doi: 10.1002/adma.201806590. Epub 2019 Jan 31.

Abstract

Glioblastoma-associated macrophages (GAMs) play a crucial role in the progression and invasiveness of glioblastoma multiforme (GBM); however, the exact crosstalk between GAMs and glioblastoma cells is not fully understood. Furthermore, there is a lack of relevant in vitro models to mimic their interactions. Here, novel 3D-bioprinted mini-brains consisting of glioblastoma cells and macrophages are presented as tool to study the interactions between these two cell types and to test therapeutics that target this interaction. It is demonstrated that in the mini-brains, glioblastoma cells actively recruit macrophages and polarize them into a GAM-specific phenotype, showing clinical relevance to transcriptomic and patient survival data. Furthermore, it is shown that macrophages induce glioblastoma cell progression and invasiveness in the mini-brains. Finally, it is demonstrated how therapeutics can inhibit the interaction between GAMs and tumor cells resulting in reduced tumor growth and more sensitivity to chemotherapy. It is envisioned that this 3D-bioprinted tumor model is used to improve the understanding of tumor biology and for evaluating novel cancer therapeutics.

Keywords: 3D bioprinting; drug screening; glioblastoma microenvironment; mini-brain; tumor-associated macrophages.

MeSH terms

  • Animals
  • Brain / pathology*
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / therapy*
  • Cell Communication*
  • Cell Line, Tumor
  • Glioblastoma / pathology*
  • Glioblastoma / therapy*
  • Humans
  • Mice
  • Printing, Three-Dimensional*
  • RAW 264.7 Cells