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.