Optimizing an Osteosarcoma-Fibroblast Coculture Model to Study Antitumoral Activity of Magnesium-Based Biomaterials

Abstract

Osteosarcoma is among the most common cancers in young patients and is responsible for one-tenth of all cancer-related deaths in children. Surgery often leads to bone defects in excised tissue, while residual cancer cells may remain. Degradable magnesium alloys get increasing attention as orthopedic implants, and some studies have reported potential antitumor activity. However, most of the studies do not take the complex interaction between malignant cells and their surrounding stroma into account. Here, we applied a coculture model consisting of green fluorescent osteosarcoma cells and red fluorescent fibroblasts on extruded Mg and Mg–6Ag with a tailored degradation rate. In contrast to non-degrading Ti-based material, both Mg-based materials reduced relative tumor cell numbers. Comparing the influence of the material on a sparse and dense coculture, relative cell numbers were found to be statistically different, thus relevant, while magnesium alloy degradations were observed as cell density-independent. We concluded that the sparse coculture model is a suitable mechanistic system to further study the antitumor effects of Mg-based material.

MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells

“…Biomaterials provide the biological structure that supports MSC osteogenic differentiation [2,[11][12][13][14][15][16][17][18]. The addition of ions has been proved to enhance the osteogenic potential of scaffolds [19].…”

Slow degrading Mg-based materials induce tumor cell dormancy on an osteosarcoma-fibroblast coculture model

“…Material surface treatment and cleaning procedure were conducted as previously described [ 10 ]. Pure Mg (99.95%) and Mg–6Ag (Mg with 6 wt % Ag) were fabricated by permanent mold gravity casting (Helmholtz-Zentrum Hereon, Geesthacht, Germany) and extrusion into rods (10 mm diameter).…”

“…The aim is to adjust the degradation rate to specifically target tumor cells and preserving the integrity of surrounding healthy cells. Therefore, we recently described an optimized osteosarcoma-fibroblast coculture model to study the antitumoral activity of Mg-based materials using fluorescent cells as a monitoring system on opaque materials [ 10 ]. Consecutive investigations focused on the tumor cytotoxicity and proliferation under normoxic and hypoxic conditions, since tumors comprise hypoxic regions, where the oxygen level fall below 3% [ [11] , [12] , [13] , [14] ].…”

Long Non-coding RNAs and MicroRNAs Interplay in Osteogenic Differentiation of Mesenchymal Stem Cells

“…MSCs are promising competent biomedical candidates in the management of several bone disorders, as their use-availability (Iaquinta et al, 2019a;Mazzoni et al, 2020a). Indeed, MSCs own several important biological properties, such as the capacity to secrete molecules that can induce tissue regeneration, selfrenewal and proliferation, as well as multipotentiality, antiinflammatory and immunomodulatory effects (Pearson et al, 2015;Batta et al, 2016;Iaquinta et al, 2019a;Globig et al, 2020;Mazzoni et al, 2020b). Isolated for the first time from the bone marrow (BM) (Bianco et al, 2008), MSCs have been subsequently harvested from many different anatomical regions, such as adipose tissue (ASCs) (Mahmoudifar and Doran, 2015;Mazzoni et al, 2020a), umbilical cord (UC-MSCs) (Galderisi and Giordano, 2014), dental pulp tissues (DPSCs) (Ferro et al, 2014), and others (Fei et al, 2013;Ferro et al, 2014;Gong et al, 2014;Fierabracci et al, 2015).…”