Biological and molecular studies in microdevices based on cancer stem cells for the development of a personalized medicine platform.

AGÜERO, IMANOL; BELGOROSKY, DENISE; PEÑAHERRERA, ANA; AZAR, MARÍA EUGENIA; CÁCERES, VALERIA; LERNER, BETIANA; PÉREZ, MAXIMILIANO S.; EIJÁN, ANA MARÍA

Mar del Plata

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2022

Sociedad Argentina de Investigación Clínica (SAIC).

The development of microfluidic devices (MD) for cancer cell research is present as new highlyversatile strategies of clinical and biological research around the world. Microfluidic-based strategies for cancer stem cells (CSC) analysis have translational relevance facilitating drugscreening, disease prognostic and other clinical applications using minimal samples andoptimizing the use of reagents. In this sense, we have developed two MDs to study CSCs bysphere forming to evaluate CSC growth, chemotherapeutic treatment (CT) response,pluripotency markers expression and to isolate CSCs derived from cancer cell lines and frombladder (BLC) and breast (BRC) cancer primary cultures. First, we analysed murine BLC MB49-Iand BRC LM38-LP cancer cell lines. Then, to validate the results, human lines J82 and BRP6(established from a patient of A. H. Roffo Institute) were used. Finally, primary cultures ofmurine tumors were studied. CSC studies in MD involved the analysis of the sphere formationefficiency (SFE), their size and their growth slope in basal condition or under CT. A significantreduction of between 30-55% in SFE (***) and 20-40% in sphere size (***) was observed withall treatments in all cell lines tested. In addition, the expression of pluripotency markers wasevaluated by qPCR and immunofluorescence (IF) within MD and more than 200% increase ofexpression was recorded in most of the analysed genes (**). As a proof of concept for thedevelopment of a platform for patient-derived CSC isolation, primary cultures of mousetumors were grown in the MD. It was possible to demonstrate the CSC growth and its responseto CT. The MD is useful to evaluate treatment response, to study specific markers by IF and toisolate cells and nucleic acids for molecular studies. The development of this technology isprojected as a useful, versatile and economic tool for estimating clinical response and as a newstrategy for personalized medicine (** p