ZVIA AGUR
	"DESTOBIO 2000" August 23-27, 2000 West Lafayette, Indiana, USA

"Effect of Local Cooperativity on Structured Systems' Homeostasis as Exemplified in a Model for Bone-Marrow Hemopoiesis"

ABSTRACT: Hemopoietic stem cells (HSC) are progenitors that can self renew and differentiate, normally yielding relatively steady amounts of blood cells of all lineages. How the conflicting forces of self renewal and differentiation are modulated is a major question, pertinent to the most critical problems in modern medicine, such as the use of growth factors in chemotherapy, gene therapy, bone marrow (BM) transplantation etc,. To improve the manipulation of HSC it is essential to understand how self-renewal and differentiation are balanced and how hemopoietic homeostasis is maintained under frequent disturbances to BM structure and function. We have constructed a relatively mathematical model of the BM, including the effect of cell-to-cell signalling on the local auto-regulation of HSC. Using this model we check how changes in the information processing of individual BM cells affect the global behaviour of the system.
The model retrieves homeostasis, in the sense that a stable average production of blood cells may be guaranteed, regardless of initial conditions, or significant BM depletion. Notably, blood counts fluctuations around the average have no characteristic scale, thus revealing the chaotic nature of this deterministic model. The most fundamental aspect of BM hemopoiesis pinpointed by our model is the multiple time-scale control of individual cells, which results from simple functional interactions in the micro-environment. We manifest the boundaries of applicability of the model by noting that an altered balance between the negative feed-back on self renewal and maturation may act as a destabilising force that can be significant in upsetting a healthy hemopoiesis structure, and in reducing its complexity in disease.

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