Growth regulation of hematopoietic cells. An overview.

The production of mature blood cells is absolutely dependent on a small pool of pluripotent stem cells with high proliferative and self-renewal capacities. The hematopoietic stem cells develop gradually from pluripotent to unipotent, committed progenitor cells during which process they lose their self-renewal capacity. This development is dependent on interactions with specific hematopoietic growth factors, which by binding to surface receptors on the stem cells stimulate them to proceed to the next step of differentiation. During recent years several of the hematopoietic growth factors have been purified to homogeneity, their primary protein as well as genetic structures have been determined and today they are available for clinical trials as recombinant proteins produced in bacteria, yeast or mammalian cells. Our present knowledge sustains the notion that IL-3, and to a lesser extent GM-CSF, play a major role in multipotent hematopoietic stem cell survival, proliferation and differentiation into stem cells with restricted maturation programs. The programmed unipotent stem cells need stimulation by erythropoietin, G-CSF, M-CSF and IL-5 to proliferate and mature into their end stage products erythrocytes, neutrophils, monocytes and eosinophils respectively. Other cytokines such as IL-1, IL-4 and IL-6 fulfil important functions as cofactors in these processes and several others play the part of tentative physiological inhibitors. During the past decade major progress has been made in our understanding of the complex interplay between stem cells, accessory cells, growth factors, and their receptors, and the clinical trials now undertaken will certainly bring even more basic knowledge to the field of hematopoietic growth regulation.