Concepts of Hemopoietic Cell Amplification. Synergy, Redundancy and Pleiotropy of Cytokines Affecting the Regulation of Erythropoiesis

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Abstract
Hemopoietic cell amplification in vivo is regulated by various mechanisms which appear to be under control of many hemopoietic growth factors. Quiescent stem cells can be activated into cell cycle, dividing progenitor cells can reduce their cell cycle time, the differentiation velocity (i.e. transit-time) can be manipulated, apoptosis can be prevented, and finally, at least in the murine system, migration of cells between the microenvironments in marrow and spleen may take place. Perturbations of any of the parameters by which these mechanisms are defined, will affect in vivo blood cell production. In this review the consequences of these perturbations, and the role of growth factors herein, are discussed. These fundamental aspects of the regulation of hemopoiesis are illustrated with recent data showing the synergistic, redundant and pleiotropic effects of SCF, IL-11, EPO and G-CSF on the in vivo formation of erythrocytes. Given the overwhelming number of growth factor-related studies that are now appearing, a re-evaluation of data, available in the literature, in the context of the mechanistic approach of growth factor-dependent hemopoiesis which is presented in this paper, seems to be useful and warranted.