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

Marcel Alexander Heinrich* (Corresponding Author), Ruchi Bansal, Twan Lammers, Yu Shrike Zhang, Raymond Michel Schiffelers, Jai Prakash (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)
138 Downloads (Pure)

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.

Original languageEnglish
Article number1806590
JournalAdvanced materials
Volume31
Issue number14
Early online date31 Jan 2019
DOIs
Publication statusPublished - 5 Apr 2019

Keywords

  • UT-Hybrid-D
  • drug screening
  • glioblastoma microenvironment
  • mini-brain
  • tumor-associated macrophages
  • 3D bioprinting

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