Modeling and simulation with Hybrid Functional Petri Nets of the role of interleukin-6 in human early haematopoiesis.

The regulation of human haematopoiesis is a complex biological system with numerous interdependent processes. In vivo Haematopoietic Stem Cells (HSCs) self-renew so as to maintain a constant pool of these cells. It would be very interesting to maintain these cells in vitro, in view of their therapeutical importance. Unfortunately, there is currently no known process to activate HSCs self-renewal in vitro. Since the difficulties related to in vitro experiments, modeling and simulating this process is indispensable. Moreover, the complexity of haematopoiesis makes it necessary to integrate various functionalities: both discrete and continuous models as well as consumption and production of resources. We thus focus on the use of Hybrid Functional Petri Nets, which offer a number of features and flexibility. We begin by modeling and simulating the role of a specific cytokine, interleukin-6, in the regulation of early haematopoiesis. Results obtained in silico lead to the disappearence of HSCs, which is in agreement with in vitro results.