A hybrid multiscale model for investigating tumor angiogenesis and its response to cell-based therapy

Abstract

Angiogenesis, a formation of blood vessels from an existing vasculature, plays a key role in tumor growth and its progression into cancer. The lining of blood vessels consists of endothelial cells (ECs) which proliferate and migrate, allowing the capillaries to sprout towards the tumor to deliver the needed oxygen. Various treatments aiming to suppress or even inhibit angiogenesis have been explored. Mesenchymal stem cells (MSCs) have recently been undergoing development in cell-based therapy for cancer due to their ability to migrate towards the capillaries and induce the apoptosis of the ECs, causing capillary degeneration. However, further investigations in this direction are needed as it is usually difficult to preclinically assess the efficacy of such therapy. We develop a hybrid multiscale model that integrates molecular, cellular, tissue and extracellular components of tumor system to investigate angiogenesis and tumor growth under MSC-mediated therapy. Our simulations produce angiogenesis and vascular tumor growth profiles as observed in the experiments. Furthermore, the simulations show that the effectiveness of MSCs in inducing EC apoptosis is density dependent and its full effect is reached within several days after MSCs application. Quantitative agreements with experimental data indicate the predictive potential of our model for evaluating the efficacy of cell-based therapies targeting angiogenesis.

Drugs modulating stochastic gene expression affect the erythroid differentiation process

“…Indeed, these effects might have several origins including modification in growth or death rates of our cells, which we cannot measure experimentally. To decipher between these effects, we decided to use a mathematical model describing the dynamics of the in vitro erythroid differentiation [39].…”

“…Every detail regarding the design, selection, calibration or identifiability analysis of our dynamic model can be found in its original paper [39]. All data and pieces of code used for the curent study are available in a public github repository https://github.com/rduchesn/Drugs-modulating-stochastic-gene-expression-affect-the-erythroid-differentiation-process.…”

“…The solution to this linear ODE model is given in the supplementary materials of the original paper [39]. We will note f i ( t j , y 0 , θ ) the prediction of this model for the i th observable of the experiment, on the j th timepoint t j , with the initial condition y 0 and parameters θ .…”

Recent Advances on Drug-Loaded Mesenchymal Stem Cells With Anti-neoplastic Agents for Targeted Treatment of Cancer

“…These cells transfer their mitochondria to endothelial cells as a subsequence of the fusion of two cells in order to shape gap junctions through connexin molecules (Otsu et al, 2009). These mitochondria are activated in the target cell and increase the production of reactive oxygen species (Hendrata and Sudiono, 2019) and induce apoptosis in endothelial cells (Otsu et al, 2009). Therefore, it seems that the antiangiogenic effect of MSCs on endothelial cells is dependent on the direct contact between these two types of cells and MSCs/endothelial cells ratio; the higher the number of MSCs, the higher endothelial cells death (Otsu et al, 2009).…”

“…Therefore, it seems that the antiangiogenic effect of MSCs on endothelial cells is dependent on the direct contact between these two types of cells and MSCs/endothelial cells ratio; the higher the number of MSCs, the higher endothelial cells death (Otsu et al, 2009). MSCs also increase the expression of caspase-3 enzyme or activate FasL-dependent pathway in endothelial cells and promote their apoptosis and in turn suppress angiogenesis (Hendrata and Sudiono, 2019).…”