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Three-dimensional constructs using hyaluronan cell carrier as a tool for the study of cancer stem cells
Cristina Martínez-Ramos1, Myriam Lebourg1,2
1Center for Biomaterials and Tissue Engineering, Universitat Politécnica de Valencia, Camino de Vera s/n, 46022, Valencia, Spain.
Background:
Cancer research focuses increasingly on cancer stem cell study as those cells are thought to be the root of chemo and radioresistance of the most aggressive cancer types. Nevertheless, two-dimensional (2D) cell culture and even three-dimensional (3D) spheroid models, with their limited ability to reflect cell-extracellular matrix interactions, are not ideal for the study of cancer stem cells (CSCs). In this study, we establish a 3D in vitro cancer model using a synthetic and natural scaffold with tunable features and show that U87 cells cultured in this system acquire a stem-cell like phenotype.
Methods:
U87 astrocytoma cells were grown on polycaprolactone (PCL)-2D flat substrates (2D) and PCL-3D scaffolds (3D) eventually containing hyaluronic acid (3D-HA). Cell viability, growth patterns, morphology, and cell surface marker expression (CD44, RHAMM and CD133) were studied to assess the effect of 3D culture and presence of HA.
Results:
3D scaffold, but most prominently presence of HA induced changes in cell morphology and marker expression; 3D-HA cultures showed features of aggregates; moreover, markedly increased expression of Nestin, CD44, RHAMM, and CD133 in 3D-HA scaffolds were found.
Conclusions:
the behavior of U87 in our 3D-HA model is more similar to tumor growth in vivo and a stem-like phenotype is promoted. Thus, the 3D-HA scaffold could provide a useful model for CSCs study and anti-cancer therapeutics research in vitro and may have preclinical application for the screening of drug candidates.
