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

N. Terranova, P. Rebuzzini, G. Mazzini, E. Borella, C. A. Redi, M. Zuccotti, S. Garagna, P. Magni

Research output: Contribution to journalArticle

Abstract

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 48. h 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.

Original languageEnglish
Pages (from-to)374-380
Number of pages7
JournalJournal of Theoretical Biology
Volume363
DOIs
Publication statusPublished - Dec 21 2014

Keywords

  • Cell death
  • Cell growth
  • Ionizing irradiation

ASJC Scopus subject areas

  • Applied Mathematics
  • Statistics and Probability
  • Modelling and Simulation
  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

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  • Cite this

    Terranova, N., Rebuzzini, P., Mazzini, G., Borella, E., Redi, C. A., Zuccotti, M., Garagna, S., & Magni, P. (2014). Mathematical modeling of growth and death dynamics of mouse embryonic stem cells irradiated with γ-rays. Journal of Theoretical Biology, 363, 374-380. https://doi.org/10.1016/j.jtbi.2014.08.042