Mathematical modeling of growth and death dynamics of mouse embryonic stem cells irradiated with γ-rays

• Published in: Journal of theoretical biology Vol. 363; pp. 374 - 380
• Main Authors: Terranova, N., Rebuzzini, P., Mazzini, G., Borella, E., Redi, C.A., Zuccotti, M., Garagna, S., Magni, P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 21.12.2014
• Subjects: Animals; Annexin A5; Apoptosis - physiology; Apoptosis - radiation effects; Cell death; Cell growth; Embryonic Stem Cells - physiology; Embryonic Stem Cells - radiation effects; G2 Phase Cell Cycle Checkpoints - physiology; G2 Phase Cell Cycle Checkpoints - radiation effects; Gamma Rays; Ionizing irradiation; Mice; Models, Biological; Time Factors; Cell death; Cell growth; Ionizing irradiation
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2014.08.042

Following ionizing radiation, mouse embryonic stem cells (mESCs) undergo both apoptosis and block at G2/M phase of the cell cycle. The dynamics of cell growth and the transition through the apoptotic phases cannot be directly inferred from experimental data, limiting the understanding of the biological response to the treatment. Here, we propose a semi-mechanistic mathematical model, defined by five compartments, able to describe the time curves of untreated and γ-rays irradiated mESCs and to extract the information therein embedded. To this end, mESCs were irradiated with 2 or 5 Gy γ-rays, collected over a period of 48h and, at each time point, analyzed for apoptosis by using the Annexin V assay. When compared to unirradiated mESCs, the model estimates an additional 0.2 probability to undergo apoptosis for the 5 Gy-treated cells, and only a 0.07 (not statistically significantly different from zero) when a 2 Gy-irradiation dose is administered. Moreover, the model allows us to estimate the duration of the overall apoptotic process and also the time length of its early, intermediate, and late apoptotic phase. •Mathematical model of growth and death dynamics of irradiated cells.•Model parameters are derived from the experimental data.•The model estimates the duration of the different phases of the apoptotic process.•Quantitation of the increased probability to undergo apoptosis after treatment.