期刊
BIOTECHNOLOGY AND BIOENGINEERING
卷 116, 期 4, 页码 936-944出版社
WILEY
DOI: 10.1002/bit.26871
关键词
cancer; microfluidics; organ-on-a-chip; three-dimensional (3D) in vitro model; tumor-on-a-chip
资金
- Wake Forest Institute for Regenerative Medicine Promoting Discoveries Pilot Program [UL1 TR001420]
Metastatic disease remains one of the primary reasons for cancer-related deaths, yet the majority of in vitro cancer models focus on the primary tumor sites. Here, we describe a metastasis-on-a-chip device that houses multiple bioengineered three-dimensional (3D) organoids, established by a 3D photopatterning technique employing extracellular matrix-derived hydrogel biomaterials. Specifically, cancer cells begin in colorectal cancer (CRC) organoid, which resides in a single microfluidic chamber connected to multiple downstream chambers in which liver, lung, and endothelial constructs are housed. Under recirculating fluid flow, tumor cells grow in the primary site, eventually enter circulation, and can be tracked via fluorescent imaging. Importantly, we describe that in the current version of this platform, HCT116 CRC cells preferentially home to the liver and lung constructs; the corresponding organs of which CRC metastases arise the most in human patients. We believe that in subsequent studies this platform can be implemented to better understand the mechanisms underlying metastasis, perhaps resulting in the identification of targets for intervention.
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