Cell-based microfluidic device for screening anti-proliferative activity of drugs in vascular smooth muscle cells
- 465 Downloads
This paper presents a microfluidic device consisting of five parallel microchambers with integrated readout-grid for the screening of anti-proliferative activity of drugs in vascular smooth muscle cells (VSMC). A two-level SU-8 master was fabricated and replicated with poly(dimethylsiloxane), PDMS, using standard soft-lithographic methods. The relative small height (4–10 μm) of the integrated grid allowed the identification of single-cells or cell groups and the monitoring of their motility, morphology and size with time, without disturbing their proliferation pattern. This is of particular interest when considering VSMC which, apart of being crucial in the atherosclerotic process, do not proliferate in a single layer but in a non-homogenous hill and valley phenotype. The performance of the microfluidic device has been validated by comparison with conventional culturing methods, proving that the cell proliferation remains unaffected by the microchamber structure (with the integrated grid) and the experimental conditions. Finally, the microfluidic device was also used to evaluate the anti-proliferative activity of curcumin and colchicine in VSMC. With this cellular type, the anti-proliferative activity of curcumin (IC50 = 35 ± 5 μM) was found to be much lower than colchicine (IC50 = 3.2 ± 1.2 μM). These results demonstrate the good performance of the microfluidic device in the evaluation of the anti-proliferative activity (or cytotoxicity) of drugs.
KeywordsMicrofluidic device Readout grid-integrated parallel microbioreactors Cell proliferation assay Vascular smooth muscle cells Antiproliferative drug delivery
The research leading to these results has received funding from the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement n° 209243. The authors would like to acknowledge the Spanish Ministry of Economy and Competitivity for the award of a Ramón y Cajal contract and the German Research Foundation (DFG) for supporting this work in the framework of the Collaborative Research Group mikroPART FOR 856 (Microsystems for particulate life-science products). This work was also supported by funds from the Ministerio de Ciencia e Innovación (AGL2009-11559) and Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía (PAIDI, CTS178), Spain. Cell culture was performed in the Biology Service of the Centro de Investigación, Tecnología e Innovación of the University of Seville (CITIUS). Authors want to acknowledge Dr. Modesto Carballo (CITIUS) for scientific support and facilities.
- J. Loukotova, L. Bacakova, J. Zicha, J. Kunes, Physiol. Res. 47, 501 (1998)Google Scholar
- S. Marasso, E. Giuri, G. Canavese, R. Castagna, M. Quaglio, I. Ferrante, D. Perrone, M. Cocuzza, Biomed. Microdevices 1 (2010)Google Scholar
- J. Martinez-Gonzalez, R. Rodriguez-Rodriguez, M. Gonzalez-Diez, C. Rodriguez, M. Herrera, V. Ruiz-Gutierrez, J. Nutr. 138, 443 (2008)Google Scholar
- H. Pae, G. Jeong, S. Jeong, H. Kim, S. Kim, Y. Kim, Korean J. Biochem. 39, 267 (2007)Google Scholar
- R. Samarakoon, P. Higgins, J. Cell Sci. 115, 3093 (2002)Google Scholar