Osteosarcoma tissue-engineered model challenges oxidative stress therapy revealing promoted cancer stem cell properties.
Por:
Tornín J, Villasante A, Solé-Martí X, Ginebra MP and Canal-Barnils C
Publicada:
20 feb 2021
Ahead of Print:
2 ene 2021
Categoría:
Biochemistry
Resumen:
The use of oxidative stress generated by Cold Atmospheric Plasma (CAP) in oncology is being recently studied as a novel potential anti-cancer therapy. However, the beneficial effects of CAP for treating osteosarcoma have mostly been demonstrated in 2-dimensional cultures of cells, which do not mimic the complexity of the 3-dimensional (3D) bone microenvironment. In order to evaluate the effects of CAP in a relevant context of the human disease, we developed a 3D tissue-engineered model of osteosarcoma using a bone-like scaffold made of collagen type I and hydroxyapatite nanoparticles. Human osteosarcoma cells cultured within the scaffold showed a high capacity to infiltrate and proliferate and to exhibit osteomimicry in vitro. As expected, we observed significantly different functional behaviors between monolayer and 3D cultures when treated with Cold Plasma-Activated Ringer's Solution (PAR). Our data reveal that the 3D environment not only protects cells from PAR-induced lethality by scavenging and diminishing the amount of reactive oxygen and nitrogen species generated by CAP, but also favours the stemness phenotype of osteosarcoma cells. This is the first study that demonstrates the negative effect of PAR on cancer stem-like cell subpopulations in a 3D biomimetic model of cancer. These findings will allow to suitably re-focus research on plasma-based therapies in future.
Filiaciones:
Tornín J:
Biomaterials, Biomechanics and Tissue Engineering Group, Department Materials Science and Metallurgy, Technical University of Catalonia (UPC), Escola D'Enginyeria Barcelona Est (EEBE), C/Eduard Maristany 14, 08019, Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, 08019, Barcelona, Spain
Research Centre for Biomedical Engineering (CREB), UPC, 08019, Barcelona, Spain
Instituto de Investigación Sanitaria Del Principado de Asturias (ISPA), Av. de Roma S/n, Oviedo, Spain
Villasante A:
Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), C/Baldiri I Reixach 10-12, 08028, Barcelona, Spain
Solé-Martí X:
Biomaterials, Biomechanics and Tissue Engineering Group, Department Materials Science and Metallurgy, Technical University of Catalonia (UPC), Escola D'Enginyeria Barcelona Est (EEBE), C/Eduard Maristany 14, 08019, Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, 08019, Barcelona, Spain
Research Centre for Biomedical Engineering (CREB), UPC, 08019, Barcelona, Spain
Ginebra MP:
Biomaterials, Biomechanics and Tissue Engineering Group, Department Materials Science and Metallurgy, Technical University of Catalonia (UPC), Escola D'Enginyeria Barcelona Est (EEBE), C/Eduard Maristany 14, 08019, Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, 08019, Barcelona, Spain
Research Centre for Biomedical Engineering (CREB), UPC, 08019, Barcelona, Spain
Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), C/Baldiri I Reixach 10-12, 08028, Barcelona, Spain
Canal-Barnils C:
Biomaterials, Biomechanics and Tissue Engineering Group, Department Materials Science and Metallurgy, Technical University of Catalonia (UPC), Escola D'Enginyeria Barcelona Est (EEBE), C/Eduard Maristany 14, 08019, Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, 08019, Barcelona, Spain
Research Centre for Biomedical Engineering (CREB), UPC, 08019, Barcelona, Spain
Open Access
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