Mathematical model of radiation effects on thrombopoiesis in rhesus macaques and humans

Abstract

A mathematical model that describes the effects of acute radiation exposure on thrombopoiesis in primates and humans is presented. Thrombopoiesis is a complex multistage dynamic process with potential differences between species. Due to known differences in cellular radiosensitivities, nadir times, and cytopenia durations, direct extrapolation from rhesus to human platelet dynamics is unrealistic. Developing mathematical models of thrombopoiesis for both humans and primates allows for the comparison of the system's response across species. Thus, data obtained in primate experiments can be extrapolated to predictions in humans. Parameter values for rhesus macaques and humans were obtained either from direct experimental measurements or through optimization procedures using dynamic data on platelet counts following radiation exposure. Model simulations accurately predict trends observed in platelet dynamics: at low radiation doses platelet counts decline after a time lag, and nadir depth is dose dependent. The models were validated using data that was not used during the parameterization process. In particular, additional experimental data was used for rhesus, and accident and platelet donor data was used for humans. The model aims to simulate the average response in rhesus and humans following irradiation. Variation in platelet dynamics due to individual variability can be modeled using Monte Carlo simulations in which parameter values are sampled from distributions. This model provides insight into the time course of the physiological effects of radiation exposure, information which could be valuable for disaster planning and survivability analysis and help in drug development of radiation medical countermeasures.

A Model for Megakaryopoiesis with State-Dependent Delay

“…Building upon previous successes reproducing the dynamics of granulopoiesis under heavy and/or repetitive stress [48], Scholz et al [49] developed a model of megakaryopoiesis under chemotherapy with successful simulations of both cell count and TPO levels [49]. Results of the same quality were obtained later by Wentz et al [54] with a model of megakaryopoiesis under radiations. Unfortunately, these last models seem, to the best of our knowledge, unfit for an extensive analytical work due the tendency to use successive compartments.…”

Ionizing Radiation Effects Modelling in Cells Population with Gold Nanoparticles

“…A few mathematical models have been derived to study the effect of ionizing radiation [14,15,16]. One of them is a mathematical model by Siam et al [8].…”

“…The modified model will consider the interaction between primary and secondary electrons by nanoparticles, which will induce double-strand breaks (DSBs) to cause lethal damage to the targeted cells. Following the simulation and experimental results in [12,14,18], we assume that the dose deposited by gold nanoparticles decreased exponentially with the size of gold nanoparticles. An experiment done by Rashid et al [20] used sphere gold nanoparticle to study the effect of ionizing radiation.…”

Parameter Estimation for a Model of Ionizing Radiation Effects on Targeted Cells using Genetic Algorithm and Pattern Search Method

“…In radiobiology, many models have been established and well studied to explain the radiation effect [7,8]. For example, Wentz et al [9] presented a mathematical model that describes the effect of acute radiation exposure on thrombopoiesis in the human body.…”