A Novel Tissue-Based Liver-Kidney-on-a-Chip Can Mimic Liver Tropism of Extracellular Vesicles Derived from Breast Cancer Cells

Abstract

Extracellular vesicles (EVs) from cancer cells remodel distant organs to promote metastasis in vivo. A biomimetic microsystem may compensate costly and time-consuming animal models to accelerate the study of EV organotropism. A tissue-based liver-kidney-on-a-chip is developed with precision-cut tissue slices (PTSs) cultured to represent individual organs. The organotropism of breast cancer EVs is modeled using the biomimetic microsystem. A traditional animal model of EV organotropism is used to investigate the physiological similarity of the microfluidic model to animal models. It is demonstrated that breast cancer EVs show strong liver tropism rather than kidney tropism on both the microfluidic and animal models. It is found that the metastatic inhibitor AMD3100 inhibits liver tropism effectively in both the microfluidic and animal models. Overall, the tropism of EVs to different organs is reconstituted on the microfluidic model. The liver-kidney-on-a-chip may expand the capabilities of traditional cell culture models and provide a faster alternative to animal models for EV studies.

Keywords: CXCL12/CXCR4; breast cancer; extraxcellular vesicles; liver tropism; microfluidic.