MODELING EX-VIVO HEMATOPOIESIS USING CHEMICAL-ENGINEERING METAPHORS

Ex vivo hematopoiesis is increasingly used for clinical applications. Models of ex vivo hematopoiesis are required to better understand the complex dynamics and to optimize hematopoietic culture processes. A ge neral mathematical modeling framework is developed which uses traditio nal chemical engineering metaphors to describe the complex hematopoiet ic dynamics. Tanks and tubular reactors are used to describe the (pseu do-) stochastic and deterministic elements of hematopoiesis, respectiv ely. Cells at any point in the differentiation process can belong to e ither an immobilized, inert phase (quiescent cells) or a mobile, activ e phase (cycling cells). The model describes five processes: (1) flow (differentiation), (2) autocatalytic formation (growth),(3) degradatio n (death), (4) phase transition from immobilized to mobile phase (quie scent to cycling transition), and (5) phase transition from mobile to immobilized phase (cycling to quiescent transition). The modeling fram ework is illustrated with an example concerning the effect of TGF-beta 1 on erythropoiesis. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.