The family of glycoproteins known as the hematopoietic growth factors (HGFs) plays a major role in the proliferation, differentiation, and survival of primitive hematopoietic stem and progenitor cells, as well as in functional activation of some mature cells. These effects are mediated by high affinity binding of the HGFs to specific receptors expressed on the surface of the target cells.
Correction or amelioration of bone marrow failure by the administration of HGFs has been and continues to be the major practical goal of research in hematopoiesis. This goal could not be achieved, however, without the early tissue culture work, which led to characterization of the hematopoietic growth factor family, and without recombinant DNA technology, which provided the genes that allowed production of purified hormones in sufficient quantities to permit interpretable in vitro and in vivo studies.
A brief review of the history of the major HGFs, the major indications for their use, and the side effects that may be seen will be presented here [1,2]. The function of specific HGFs — such as erythropoietin, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and thrombopoietin — in the regulation of erythropoiesis, myelopoiesis, and megakaryocytopoiesis, respectively, are discussed in detail elsewhere. (See "Overview of hematopoiesis and stem cell function" and "Regulation of erythropoiesis" and "Regulation of myelopoiesis" and "Megakaryocyte biology and the production of platelets".)
Beginning with pioneering studies in the early 1960s, it has been recognized that normal and leukemic blood progenitor cells can be propagated in semisolid culture in the presence of soluble growth factors [3,4]. These factors were originally termed colony-stimulating factors (CSFs) because of their ability to support the formation of colonies of blood cells by bone marrow cells plated in semisolid medium .
During the 1970s and 1980s, it became clear that there were multiple types of CSFs based upon the different types of colonies that grew in the presence of the different factors. This observation led to the hypothesis that the growth and differentiation of blood cells were controlled, at least in part, by exposure of progenitor cells to CSFs having different lineage specificities [5,6].