Advancing breast cancer research through the development of a macrophage-containing bioink

Details

Supervisors

Pierreux, Christophe ; Demoustier-Champagne, Sophie

Faculty

Ecole polytechnique de Louvain

Degree label

Master [120] : ingénieur civil biomédical, à finalité spécialisée

Abstract

Completely eradicating breast cancer cells, particularly in the dominant breast cancer subtype, remains a significant challenge when treated with neoadjuvant chemotherapy due to frequent drug resistance. There is thus an urgent need for innovative and more effective treatments, which target cancer cells while also accounting for the influence of the microenvironment. For this purpose, developing an in vitro model that mimics in vivo cell-microenvironment interactions to study breast cancer and its resistance to treatment is paramount. The aim of this thesis is to extend the in vitro breast cancer model developed at the de Duve Institute. The current model uses an alginate-gelatin hydrogel in which MCF7 breast cancer cells are embedded. To better reproduce the tumor microenvironment, other cell types, such as tumor-associated macrophages, need to be incorporated into the hydrogel. Therefore, the objective of this master’s thesis is to study the survival, proliferation and differentiation of THP1 monocytes -- precursors of macrophages -- within the alginate-gelatin hydrogel. THP1 monocytes, cultured in suspension, were embedded within the alginate-gelatin hydrogel to create THP1 hydrogel-embedded spheroids. Diameter measurements, viability assessments and quantitative polymerase chain reactions were performed to determine the fate of THP1 monocytes within the hydrogel. The results demonstrated that, after an initial crisis leading to cell death upon embedding, THP1 monocytes adapted to their environment, survived, proliferated and differentiated within the alginate-gelatin hydrogel. Further research should address the issue of initial mortality, explore the fate of THP1 monocytes co-embedded with MCF7 breast cancer cells within the hydrogel and ultimately test the effect of neoadjuvant chemotherapy treatment. Furthermore, the suitability of the hydrogel as a bioink should be investigated using a 3D bioprinter.