## Section: Scientific Foundations

### Delay differential Equations

Delay differential equations (DDEs) are particularly useful for situations where the processes are controlled through feedback loops acting after a certain time. For example, in the evolution of cell populations the transmission of control signals can be related to some processes as division, differentiation, maturation, apoptosis, etc. Because these processes can take a certain time, the system depends on an essential way of its past state, and can be modelled by DDEs.

We explain hereafter how delays can appear in hematopoietic models. Based on biological aspects, we can divide hematopoietic cell populations into many compartments. We basically consider two different cell populations, one composed with immature cells, and the other one made of mature cells. Immature cells are separated in many stages (primitive stem cells, progenitors and precursors, for example) and each stage is composed with two sub-populations, resting (G0) and proliferating cells. On the opposite, mature cells are known to proliferate without going into the resting compartment. Usually, to describe the dynamic of these multi-compartment cell populations, transport equations (hyperbolic PDEs) are used. Structure variables are age and discrete maturity. In each proliferating compartment, cell count is controlled by apoptosis (programmed cell death), and in the other compartments, cells can be eliminated only by necrosis (accidental cell death). Transitions between the compartments are modelled through boundary conditions. In order to reduce the complexity of the system and due to some lack of information, no dependence of the coefficients on cell age is assumed. Hence, the system can be integrated over the age variable and thus, by using the method of characteristics and the boundary conditions, the model reduces to a system of DDEs, with several delays.

Leaving all continuous structures, DDEs appear well adapted to us to describe the dynamics of cell populations. They offer good tools to study the behaviour of the systems. The main investigation of DDEs are the effect of perturbations of the parameters, as cell cycle duration, apoptosis, differentiation, self-renewal, and re-introduction from quiescent to proliferating phase, on the behaviour of the system, in relation for instance with some hematological disorders [29] .