期刊
CELL REPORTS
卷 26, 期 3, 页码 608-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.12.090
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资金
- NIH [R01 CA196228]
- NIH U54 grant [CA209988]
- SBIR phase I contract [HHSN261201400024C]
- Collins Medical Trust
- Knight Cancer Institute through NIH P30 grant [CA69533]
The tumor microenvironment plays a critical role in tumor growth, progression, and therapeutic resistance, but interrogating the role of specific tumor-stromal interactions on tumorigenic phenotypes is challenging within in vivo tissues. Here, we tested whether three-dimensional (3D) bioprinting could improve in vitro models by incorporating multiple cell types into scaffold-free tumor tissues with defined architecture. We generated tumor tissues from distinct subtypes of breast or pancreatic cancer in relevant microenvironments and demonstrate that this technique can model patient-specific tumors by using primary patient tissue. We assess intrinsic, extrinsic, and spatial tumorigenic phenotypes in bio-printed tissues and find that cellular proliferation, extracellular matrix deposition, and cellular migration are altered in response to extrinsic signals or therapies. Together, this work demonstrates that multi-cell-type bioprinted tissues can recapitulate aspects of in vivo neoplastic tissues and provide a manipulable system for the interrogation of multiple tumorigenic endpoints in the context of distinct tumor microenvironments.
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