Computational modeling of multiple myeloma interactions with resident bone marrow cells.

The interaction of multiple myeloma with bone marrow resident cells plays a key role in tumor progression and the development of drug resistance. The tumor cell response involves contact-mediated and paracrine interactions. The heterogeneity of myeloma cells and bone marrow cells makes it difficult to reproduce this environment in in-vitro experiments. The use of in-silico established tools can help to understand these complex problems. In this article, we present a computational model based on the finite element method to define the interactions of multiple myeloma cells with resident bone marrow cells. This model includes cell migration, which is controlled by stress-strain equilibrium, and cell processes such as proliferation, differentiation, and apoptosis. A series of computational experiments were performed to validate the proposed model. Cell proliferation by the growth factor IGF-1 is studied for different concentrations ranging from 0-10 ng/mL. Cell motility is studied for different concentrations of VEGF and fibronectin in the range of 0-100 ng/mL. Finally, cells were simulated under a combination of IGF-1 and VEGF stimuli whose concentrations are considered to be dependent on the cancer-associated fibroblasts in the extracellular matrix. Results show a good agreement with previous in-vitro results. Multiple myeloma growth and migration are shown to correlate linearly to the IGF-1 stimuli. These stimuli are coupled with the mechanical environment, which also improves cell growth. Moreover, cell migration depends on the fiber and VEGF concentration in the extracellular matrix. Finally, our computational model shows myeloma cells trigger mesenchymal stem cells to differentiate into cancer-associated fibroblasts, in a dose-dependent manner.

Enhanced Piezoelectric Fibered Extracellular Matrix to Promote Cardiomyocyte Maturation and Tissue Formation: A 3D Computational Model.

Mechanical and electrical stimuli play a key role in tissue formation, guiding cell processes such as cell migration, differentiation, maturation, and apoptosis. Monitoring and controlling these stimuli on in vitro experiments is not straightforward due to the coupling of these different stimuli. In addition, active and reciprocal cell-cell and cell-extracellular matrix interactions are essential to be considered during formation of complex tissue such as myocardial tissue. In this sense, computational models can offer new perspectives and key information on the cell microenvironment. Thus, we present a new computational 3D model, based on the Finite Element Method, where a complex extracellular matrix with piezoelectric properties interacts with cardiac muscle cells during the first steps of tissue formation. This model includes collective behavior and cell processes such as cell migration, maturation, differentiation, proliferation, and apoptosis. The model has employed to study the initial stages of in vitro cardiac aggregate formation, considering cell-cell junctions, under different extracellular matrix configurations. Three different cases have been purposed to evaluate cell behavior in fibered, mechanically stimulated fibered, and mechanically stimulated piezoelectric fibered extra-cellular matrix. In this last case, the cells are guided by the coupling of mechanical and electrical stimuli. Accordingly, the obtained results show the formation of more elongated groups and enhancement in cell proliferation.