Open AccessThree-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions
Author(s) -
Min Tang,
Qi Xie,
Ryan C. Gimple,
Zheng Zhong,
Trevor Tam,
Jing Tian,
Reilly L. Kidwell,
Qiulian Wu,
Briana C. Prager,
Zhixin Qiu,
Aaron Yu,
Zhe Zhu,
Pinar Mesci,
Hui Jing,
Jacob Schimelman,
Pengrui Wang,
Derrick Lee,
Michael H. Lorenzini,
Deobrat Dixit,
Linjie Zhao,
Shruti Bhargava,
Tyler E. Miller,
Xueyi Wan,
Jing Tang,
Bingjie Sun,
Benjamin F. Cravatt,
Alysson R. Muotri,
Shaochen Chen,
Jeremy Rich
Publication year - 2020
Publication title -
cell research/cell research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.395
H-Index - 167
eISSN - 1748-7838
pISSN - 1001-0602
DOI - 10.1038/s41422-020-0338-1
Subject(s) - tumor microenvironment , glioblastoma , biology , 3d bioprinting , immune system , multicellular organism , microglia , context (archaeology) , computational biology , neuroscience , cancer research , cell , immunology , tissue engineering , inflammation , genetics , paleontology
Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.