Microdevices for cancer stem cell culture as a predictive chemotherapeutic response platform.

Abstract

Microfluidic platforms for clinical use are a promising translational strategy for cancer research specially for drug screening. Identifying cancer stem cells (CSC) using sphere culture techniques in microfluidic devices (MDs) showed to be better reproducing physiological responses than other in vitro models and allow the optimization of samples and reagents. We evaluated individual sphere proliferation and stemness toward chemotherapeutic treatment (CT) with doxorubicin and cisplatin in bladder cancer cell lines (MB49-I and J82) cultured in MDs used as CSC treatment response platform. Our results confirm the usefulness of this device to evaluate the CT effect in sphere-forming efficiency, size, and growth rate from individual spheres within MDs and robust information comparable to conventional culture plates was obtained. The expression of pluripotency genetic markers (Oct4, Sox2, Nanog, and CD44) could be analyzed by qPCR and immunofluorescence in spheres growing directly in MDs. MDs are a suitable platform for sphere isolation from tumor samples and can provide information about CT response. Microfluidic-based CSC studies could provide information about treatment response of cancer patients from small samples and can be a promising tool for CSC-targeted specific treatment with potential in precision medicine. KEY MESSAGES: We have designed a microfluidic platform for CSC enriched culture by tumor sphere formation. Using MDs, we could quantify and determine sphere response after CT using murine and human cell lines as a proof of concept. MDs can be used as a tumor-derived sphere isolation platform to test the effect of antitumoral compounds in sphere proliferation.