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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.


Fraction of apoptotic cells obtained from simulations (dotted lines) and from experimental data (solid lines) for 24 and 48 hours.
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fig3: Fraction of apoptotic cells obtained from simulations (dotted lines) and from experimental data (solid lines) for 24 and 48 hours.

Mentions: We run the simulations with secretome concentration varied from 0.2%, 2%, and 20% under 24- and 48-hour treatments, giving a total of six simulation scenarios. We run each simulation scenario 100 times using the apoptosis threshold value A = 0.7. The mean and standard deviation are computed and they are plotted as simulation data point and error bar in Figure 3(b).


A Computational Model for Investigating Tumor Apoptosis Induced by Mesenchymal Stem Cell-Derived Secretome
Fraction of apoptotic cells obtained from simulations (dotted lines) and from experimental data (solid lines) for 24 and 48 hours.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Fraction of apoptotic cells obtained from simulations (dotted lines) and from experimental data (solid lines) for 24 and 48 hours.
Mentions: We run the simulations with secretome concentration varied from 0.2%, 2%, and 20% under 24- and 48-hour treatments, giving a total of six simulation scenarios. We run each simulation scenario 100 times using the apoptosis threshold value A = 0.7. The mean and standard deviation are computed and they are plotted as simulation data point and error bar in Figure 3(b).

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.