HE GENERATION OF functional cells of the hemato-T poietic system is an enormously complex enterprise requiring both the constant production of large numbers of differentiated cells and the maintenance of primitive precursors throughout the lifetime of the individual. Our understanding of the mechanisms of control of this process is still rudimentary, but has increased significantly over the last three decades. It is now clear that a number of glycoproteins play an important role in the self-renewal, amplification, and differentiation of hematopoietic cells. Combinations of several glycoprotein growth factors are shown in this issue of Blood to effect large increases in the number of progenitor cells when cultured ex vivo. The report by Muench et al’represents an example of the potential for basic investigations into hematopoietic stem cell biology to have direct applications in clinical medicine. Although our understanding of the hematopoietic stem cell compartment is still limited, research by many groups has led to an emerging consensus about these rare and important cells. Stem cells are heterogeneous with respect to size, density, antigenic profile, and function. In the steady state, the vast majority of stem cells are not in active cell cycle. The most primitive cells appear to require multiple growth factors to acquire by survival and differentiation the ability to respond to single growth factors. This transition from a primitive stem cell to functional cells of the hematopoietic system occurs via a number of intermediate stages characterized by progressive loss of self-renewal capacity and progressive lineage restriction, a process termed commitment. Amplification (ie, increase in cell numbers) of hematopoietic cells occurs in late stages of this process, when cells are mostly committed to one lineage. These concepts have been established using a number of ingenious methods established by distinguished investigators in the field of experimental hematopoiesis.

The ability to grow bone marrow cells in clonogenic assays, first described by Pluznik and Sachs2 and Metcalf and Bradley3 was a decisive step in elucidating characteristics of the differentiated progeny of stem cells, termed progenitor cells. In addition, this observation in later years allowed for the purification and cloning of several colony-stimulating factors, which have now had a major impact on clinical