Microfluidic devices to analyze the response of sphere-forming stem-like populations to chemotherapeutic drugs

Author:

Agüero Eduardo Imanol1,Belgorosky Denise1,García-Silva Julio Israel2,Booth Ross3,Lerner Betiana4,Pérez Maximiliano Sebastián5,Eiján Ana María6ORCID

Affiliation:

1. Institute of Oncology Angel H Roffo: Instituto de Oncologia Angel H Roffo

2. CONICET: Consejo Nacional de Investigaciones Cientificas y Tecnicas

3. Florida International University College of Engineering & Computing

4. Universidad de Buenos Aires Facultad de Ingeneria

5. Colaborative Research Institute Intelligent Oncology (CRIION)

6. Instituto de Oncologia Angel H Roffo

Abstract

Abstract Microfluidic platforms for clinical use are a promising translational strategy for cancer research specially for drug screening. Identifyng 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 spheres proliferation and stemness towards 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.

Publisher

Research Square Platform LLC

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