  The production and regulation of red blood cells, erythropoiesis, occurs in
the bone marrow where erythroid cells proliferate and differentiate within
particular structures, called erythroblastic islands. A typical structure of
these islands consists in a macrophage (white cell) surrounded by immature
erythroid cells (progenitors), with more mature cells on the periphery of the
island, ready to leave the bone marrow and enter the bloodstream. A hybrid
model, coupling a continuous model (ordinary differential equations) describing
intracellular regulation through competition of two key proteins, to a discrete
spatial model describing cell-cell interactions, with growth factor diffusion
in the medium described by a continuous model (partial differential equations),
is proposed to investigate the role of the central macrophage in normal
erythropoiesis. Intracellular competition of the two proteins leads the
erythroid cell to either proliferation, differentiation, or death by apoptosis.
This approach allows considering spatial aspects of erythropoiesis, involved
for instance in the occurrence of cellular interactions or the access to
external factors, as well as dynamics of intracellular and extracellular scales
of this complex cellular process, accounting for stochasticity in cell cycle
durations and orientation of the mitotic spindle. The analysis of the model
shows a strong effect of the central macrophage on the stability of an
erythroblastic island, when assuming the macrophage releases pro-survival
cytokines. Even though it is not clear whether or not erythroblastic island
stability must be required, investigation of the model concludes that stability
improves responsiveness of the model, hence stressing out the potential
relevance of the central macrophage in normal erythropoiesis.
