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Modelling hematopoiesis in health and disease
Authors:Diogo Peixoto  David Dingli  Jorge M Pacheco
Institution:1. ATP-Group, CMAF, Av. Prof. Gama Pinto 2, 1649-003 Lisboa, Portugal;2. Division of Hematology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA;3. Departamento de Matemática e Aplicações, Universidade do Minho, 4710-057 Braga, Portugal
Abstract:Hematopoiesis is the process responsible for maintaining the number of circulating blood cells that are undergoing continuous turnover. At the root of this process are the hematopoietic stem cells (HSC), that replicate slowly to self-renew and give rise to progeny cells that proceed along the path of differentiation. The process is complex, with the cells responding to a wide variety of cytokines and growth factors. We discuss the mathematics of hematopoiesis based on stochastic cell behavior. Multiple compartments are introduced to keep track of each cell division process and increasing differentiation. The same mathematical model that describes normal hematopoiesis across mammals as a stable steady state of a hierarchical stochastic process is also used to understand the detailed dynamics of various disorders both in humans and in animal models. The microecology of the multitude of cell lineages that constitute what we call troubled hematopoiesis evolves in time under mutation and selection, the paradigmatic components of Darwinian evolution. Thus, the present approach provides a novel perspective for looking at cancer progression and cure.
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