Microfluidic device engineered to study the trafficking of multiple myeloma cancer cells through the sinusoidal niche of bone marrow

Chao Sui, Jenny Zilberberg, Woo Lee

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Multiple myeloma (MM) is an incurable B cell malignancy characterized by the accumulation of monoclonal abnormal plasma cells in the bone marrow (BM). It has been a significant challenge to study the spatiotemporal interactions of MM cancer cells with the embedded microenvironments of BM. Here we report a microfluidic device which was designed to mimic several physiological features of the BM niche: (1) sinusoidal circulation, (2) sinusoidal endothelium, and (3) stroma. The endothelial and stromal compartments were constructed and used to demonstrate the device’s utility by spatiotemporally characterizing the CXCL12-mediated egression of MM cells from the BM stroma and its effects on the barrier function of endothelial cells (ECs). We found that the egression of MM cells resulted in less organized and loosely connected ECs, the widening of EC junction pores, and increased permeability through ECs, but without significantly affecting the number density of viable ECs. The results suggest that the device can be used to study the physical and secreted factors determining the trafficking of cancer cells through BM. The sinusoidal flow feature of the device provides an integral element for further creating systemic models of cancers that reside or metastasize to the BM niche.

Original languageEnglish
Article number1439
JournalScientific Reports
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

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