Stability analysis of models of cell production systems

We investigate the qualitative behaviour of the models of cell production systems, in the form of systems of nonlinear delay differential equations. Considered are three general models of a system involving the subpopulations of stem cells, precursor cells and mature cells, with different configurations of regulation feedbacks. The models correspond basically to the blood cell production process; however, other applications are possible. First, the simplified version (describable by ordinary differential equations) is considered. Fairly complete characterization of the trajectories is possible in this case, using the Lyapunov functions and phase plane techniques. Next, for the general models, the stability of equations linearized around the equilibria is investigated. Certain results can be obtained here, using both exact methods and numerical procedures based on an original lemma on the zeros of exponential polynomials. Then global properties (boundedness, attractivity, etc.) are examined for the nonlinear, delay case using a range of methods: Lyapunov functionals, Razumikhin functions and direct estimates on solutions. Certain special cases of our models reduce to previous literature models of blood production. Results of our analysis enable to exclude these configurations of regulation feedbacks which yield model behaviour not compatible with biological and medical observations. Techniques developed in this paper are applicable to a wide range of possible models of cell production systems.