Abstract:
: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.
journal_name
Cell Resjournal_title
Cell researchauthors
Tang M,Xie Q,Gimple RC,Zhong Z,Tam T,Tian J,Kidwell RL,Wu Q,Prager BC,Qiu Z,Yu A,Zhu Z,Mesci P,Jing H,Schimelman J,Wang P,Lee D,Lorenzini MH,Dixit D,Zhao L,Bhargava S,Miller TE,Wan X,Tang J,Sun B,Cravattdoi
10.1038/s41422-020-0338-1subject
Has Abstractpub_date
2020-10-01 00:00:00pages
833-853issue
10eissn
1001-0602issn
1748-7838pii
10.1038/s41422-020-0338-1journal_volume
30pub_type
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