Modelling and Asymptotic Stability of a Growth Factor-Dependent Stem Cells Dynamics Model with Distributed Delay ⁄

Under the action of growth factors, proliferating and nonproliferating hematopoietic stem cells differentiate and divide, so as to produce blood cells. Growth factors act at different levels in the differentiation process, and we consider their action on the mortality rate (apoptosis) of the proliferating cell population. We propose a mathematical model describing the evolution of a hematopoietic stem cell population under the action of growth factors. It consists of a system of two age-structured evolution equations modelling the dynamics of the stem cell population coupled with a delay differential equation describing the evolution of the growth factor concentration. We first reduce our system of three differential equations to a system of two nonlinear differential equations with two delays and a distributed delay. We investigate some positivity and boundedness properties of the solutions, as well as the existence of steady states. We then analyze the asymptotic stability of the two steady states by studying the characteristic equation with delay-dependent coefficients obtained while linearizing our system. We obtain necessary and sufficient conditions for the global stability of the steady state describing the cell population's dying out, using a Lyapunov function, and we prove the existence of periodic solutions about the other steady state through the existence of a Hopf bifurcation.