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Adv Mater. 2019 Jan 31:e1806590. doi: 10.1002/adma.201806590. [Epub ahead of print]

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

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Department of Biomaterials Science and Technology, Targeted Therapeutics Section, Technical Medical Centre, University of Twente, 7500 AE, Enschede, The Netherlands.
Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, 52074, Aachen, Germany.
Division of Engineering in Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Cambridge, MA, 02139, USA.
Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, 3584, CX Utrecht, The Netherlands.


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.


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


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