A multi‐site metastasis‐on‐a‐chip microphysiological system for assessing metastatic preference of cancer cells

• Published in: Biotechnology and bioengineering Vol. 116; no. 4; pp. 936 - 944
• Main Authors: Aleman, Julio, Skardal, Aleksander
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2019
• Subjects: A549 Cells; Bioengineering; Biomaterials; Biomedical materials; Cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnostic imaging; Colorectal Neoplasms - pathology; Computational fluid dynamics; Equipment Design; Extracellular matrix; Fluid flow; Fluorescence; Fluoroscopic imaging; HCT116 Cells; Hep G2 Cells; Human Umbilical Vein Endothelial Cells; Humans; Hydrogels; Lab-On-A-Chip Devices; Liver; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - secondary; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - secondary; Lungs; Metastases; Metastasis; Microfluidics; Optical Imaging; Organoids; Organoids - diagnostic imaging; Organoids - pathology; Organs; organ‐on‐a‐chip; Target recognition; three‐dimensional (3D) in vitro model; Tumor cells; Tumors; tumor‐on‐a‐chip; cancer; organ-on-a-chip; microfluidics; three-dimensional (3D) in vitro model; tumor-on-a-chip
• ISSN: 0006-3592; 1097-0290; 1097-0290
• DOI: 10.1002/bit.26871

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. 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.