IBEC Seminar: Maria Virumbrales

“Development of microfluidic tools to reproduce and characterize the tumor microenvironment”

Compelling evidence over the years has demonstrated that the tumor microenvironment (TME) shapes tumor initiation, development and response to therapy. This results in a high heterogeneity within the same cancer type, and hinders the process of finding effective treatments.[1,2]

In this context, microfluidics has proven a worthy sum of techniques to create comprehensive and personalized cancer in vitro 3D models reproducing the TME in a more relevant fashion than traditional in vitro setups.

Microfluidics also permits a high degree of control over the setup, combining different cell types in an orderly manner, as well as different physical and biochemical cues. [3] Furthermore, microfluidics facilitates optical inspection and diminishes sample sizes and reagent volumes needed for each experiment. Microfluidic devices are also compatible with high-throughput approaches, which make them an interesting option for drug testing, research and development.[4]

Hence, we developed two microfluidic tumor models, which we used to model and characterize different aspects of the TME. TME was characterized in terms of hypoxia, proliferation rates, reactive oxygen species concentration, apoptosis rate and glucose uptake.[5] Moreover, the influence of tumor cells on an endothelium was investigated. Furthermore, we carried out pharmacodynamic and drug efficiency studies in these newly-established models. Thereafter, we developed a simple enzymatic protocol to extract cells seeded in 3D from the microfluidic devices. Cells could be sorted by flow cytometry according to the expression of specific surface markers or by using different fluorescent stains. RNA was extracted for downstream quantification and gene profiling was carried out for the mentioned aspects of the tumor microenvironment.

All in all, we developed two easy-to-use microfluidic models for personalized medicine capable of comprehensive reproduction of the TME, which allows characterization of tumor signatures by means of microscopy and traditional benchtop methods.

1. Balkwill FR, Capasso M, Hagemann T (2012) The tumor microenvironment at a glance. J Cell Sci 125: 5591-5596.
2. Klemm F, Joyce JA (2015) Microenvironmental regulation of therapeutic response in cancer. Trends Cell Biol 25: 198-213.
3. Sackmann EK, Fulton AL, Beebe DJ (2014) The present and future role of microfluidics in biomedical research. Nature 507: 181-189.
4. Du G, Fang Q, den Toonder JMJ (2016) Microfluidics for cell-based high throughput screening platforms—A review. Analytica Chimica Acta 903: 36-50.
5. Ayuso JM, Virumbrales-Munoz M, Lacueva A, Lanuza PM, Checa-Chavarria E, et al. (2016) Development and characterization of a microfluidic model of the tumour microenvironment. Sci Rep 6: 36086.

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