A mathematical model for cell differentiation, as an evolutionary and regulated process

We introduce an approach which allows one to introduce the concept of cell plasticity into models for tissue regeneration. In contrast to most of the recent models for tissue regeneration, cell differentiation is considered a gradual process, which evolves in time and which is regulated by an arbitrary number of parameters. In the current approach, cell differentiation is modelled by means of a differentiation state variable. Cells are assumed to differentiate into an arbitrary number of cell types. The differentiation path is considered as reversible, unless differentiation has fully completed. Cell differentiation is incorporated into the partial differential equations (PDEs), which model the tissue regeneration process, by means of an advection term in the differentiation state space. This allows one to consider the differentiation path of cells, which is not possible if a reaction-like term is used for differentiation. The boundary conditions, which should be specified for the general PDEs, are derived from the flux of the fully non-differentiated cells and from the irreversibility of the fully completed differentiation process. An application of the proposed model for peri-implant osseointegration is considered. Numerical results are compared with experimental data. Potential lines of further development of the present approach are proposed.