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Cancer Technologies

Engineered Cancer Models for In Vitro Studies II

Multi-organ Microfluidic Model for Breast Cancer Metastasis

Friday, October 13, 2023
5:15 PM – 5:30 PM PDT
Location: 337 (Center, Level 3)
Introduction:: Breast cancer metastasis occurs when cancer cells originating from the breast tissue spread to other parts of the body through the bloodstream or lymphatic system, resulting in the formation of secondary tumors. This spread is a leading cause of breast cancer-related deaths. Breast cancer metastasis exhibits a marked preference for certain organs, with the liver, lungs, brain, and bones being the primary sites of metastasis. The cellular and molecular mechanisms driving this highly dynamic, organ-specific process are not fully understood due to the lack of relevant human disease models capturing the complexity of breast cancer metastasis and its organotropism. Emerging Body-on-a-Chip technologies that integrate multiple organ and tissue biomimics in a microfluidic device hold great potential to simulate the dynamic disease progression of human breast cancer metastasis in vitro. This study aims to create a multi-organ microfluidic model based on human cells that integrates 3D microtissues representing primary metastasis sites of breast cancer and circulating cancer cells, enabling the interaction between them and facilitating future mechanistic study and drug testing in vitro.

Materials and Methods:: We developed a microfluidic system with organ chambers representing the brain, bone, liver, and lung. The dimensions of the organ chambers and the perfusion channels were designed using residence time-based scaling to maintain physiological conditions on chip. Medium recirculation of the system was achieved using a UniChip design for continuous unidirectional perfusion in a gravity-driven flow system. The microfluidic device was fabricated using a combination of 3D printing, soft lithography, and laser patterning techniques, and its fluid dynamics were validated using computational simulation and flow characterization experiments using particle tracking. The device’s ability to sustain dynamic 3D tissue cultures was assessed through morphological analysis of cells, live-dead cell staining, and lactate dehydrogenase assay for a period of up to 7 days. Breast cancer cells were added into circulating medium to enable breast cancer interaction with multi-organ cultures.

Results, Conclusions, and Discussions:: The flow rates characterized with particle tracking aligned with the design values and the simulation results for different organ units. 7 day dynamics culture experiments demonstrated reliable survival and proliferation of different types of cells representing various organs on the chip. We also successfully integrated fluorescent-labeled human breast cancer cells into the perfusion medium and maintained their circulation for 24 hours, enabling metastatic cancer cell tracking experiments. The system will further be utilized for mechanism studies on the interactions between circulating breast cancer cells and the organ-specific microenvironment.


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