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

J Theor Biol. 2014 Dec 21:363:374-80. doi: 10.1016/j.jtbi.2014.08.042. Epub 2014 Sep 4.

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.

Keywords: Cell death; Cell growth; Ionizing irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5
  • Apoptosis / physiology*
  • Apoptosis / radiation effects
  • Embryonic Stem Cells / physiology*
  • Embryonic Stem Cells / radiation effects
  • G2 Phase Cell Cycle Checkpoints / physiology*
  • G2 Phase Cell Cycle Checkpoints / radiation effects
  • Gamma Rays*
  • Mice
  • Models, Biological*
  • Time Factors

Substances

  • Annexin A5