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A Computational Model for Investigating Tumor Apoptosis Induced by Mesenchymal Stem Cell-Derived Secretome

View Article: PubMed Central - PubMed

ABSTRACT

Apoptosis is a programmed cell death that occurs naturally in physiological and pathological conditions. Defective apoptosis can trigger the development and progression of cancer. Experiments suggest the ability of secretome derived from mesenchymal stem cells (MSC) to induce apoptosis in cancer cells. We develop a hybrid discrete-continuous multiscale model to further investigate the effect of MSC-derived secretome in tumor growth. The model encompasses three biological scales. At the molecular scale, a system of ordinary differential equations regulate the expression of proteins involved in apoptosis signaling pathways. At the cellular scale, discrete equations control cellular migration, phenotypic switching, and proliferation. At the extracellular scale, a system of partial differential equations are employed to describe the dynamics of microenvironmental chemicals concentrations. The simulation is able to produce both avascular tumor growth rate and phenotypic patterns as observed in the experiments. In addition, we obtain good quantitative agreements with the experimental data on the apoptosis of HeLa cancer cells treated with MSC-derived secretome. We use this model to predict the growth of avascular tumor under various secretome concentrations over time.

No MeSH data available.


Flowchart showing the integration of molecular, cellular, and extracellular scales into a sequence of events executed at each iteration. The molecular level processes are shown in yellow, extracellular level process is shown in blue, and cellular level processes are shown in green.
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fig2: Flowchart showing the integration of molecular, cellular, and extracellular scales into a sequence of events executed at each iteration. The molecular level processes are shown in yellow, extracellular level process is shown in blue, and cellular level processes are shown in green.

Mentions: The integration of the molecular, cellular, and extracellular time scales and the sequence of steps computed by a cell at each iteration are illustrated in the flowchart in Figure 2. In the flowchart, the molecular level processes are colored in yellow, the extracellular process in blue, and the cellular level processes in green.


A Computational Model for Investigating Tumor Apoptosis Induced by Mesenchymal Stem Cell-Derived Secretome
Flowchart showing the integration of molecular, cellular, and extracellular scales into a sequence of events executed at each iteration. The molecular level processes are shown in yellow, extracellular level process is shown in blue, and cellular level processes are shown in green.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120213&req=5

fig2: Flowchart showing the integration of molecular, cellular, and extracellular scales into a sequence of events executed at each iteration. The molecular level processes are shown in yellow, extracellular level process is shown in blue, and cellular level processes are shown in green.
Mentions: The integration of the molecular, cellular, and extracellular time scales and the sequence of steps computed by a cell at each iteration are illustrated in the flowchart in Figure 2. In the flowchart, the molecular level processes are colored in yellow, the extracellular process in blue, and the cellular level processes in green.

View Article: PubMed Central - PubMed

ABSTRACT

Apoptosis is a programmed cell death that occurs naturally in physiological and pathological conditions. Defective apoptosis can trigger the development and progression of cancer. Experiments suggest the ability of secretome derived from mesenchymal stem cells (MSC) to induce apoptosis in cancer cells. We develop a hybrid discrete-continuous multiscale model to further investigate the effect of MSC-derived secretome in tumor growth. The model encompasses three biological scales. At the molecular scale, a system of ordinary differential equations regulate the expression of proteins involved in apoptosis signaling pathways. At the cellular scale, discrete equations control cellular migration, phenotypic switching, and proliferation. At the extracellular scale, a system of partial differential equations are employed to describe the dynamics of microenvironmental chemicals concentrations. The simulation is able to produce both avascular tumor growth rate and phenotypic patterns as observed in the experiments. In addition, we obtain good quantitative agreements with the experimental data on the apoptosis of HeLa cancer cells treated with MSC-derived secretome. We use this model to predict the growth of avascular tumor under various secretome concentrations over time.

No MeSH data available.