Myelo-lymphopoietic stem cells in human bone marrow

Normal hemopoiesis is dependent upon the appropriate function of pluripotent stem cells. These primitive progenitors are characterized by their ability to proliferate extensively and to mature along the various pathways of hemopoietic differentiation. Their self-renewal capacity ensures the propagation of the system. In addition it is mandatory that these stem cells are responsive to regulatory mechanisms in order to adjust their activity to varying demands [22]. Pluripotent stem cells were first identified and quantitated by Till and McCulloch using their well established spleen colony assay (CFU-S) [34]. This method facilitated investigations that led to some understanding of mechanisms regulating the activity of stem ceils. When the assay was used to assess bone marrow of two strains of genetically anemic mice (W/W ~ and S1/S1 d) two defects could be identified leading to the development of anemia. In animals of the one strain (W/W v) the defect was found to be endogenous to the pluripotent stem cells and readily correctable by stem cell transplantation [24]. In animals of the other strain (S1/SF) a defective supporting environment could be identified which was only correctable by transplantation of whole spleens [23]. In man clinical conditions such as chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and Polycythemia rubra vera (PV) are now considered to originate in defective stem cells. This information was essentially provided by studies carried out by Fialkow and his co-workers on such patients that were also heterozygous for the X-linked marker enzyme G-6-PD [2, 15, 19]. This method permitted the investigations to trace cells carrying the disease phenotype back to common ancestors, indicating the clonal nature of these disorders. In order to assess mechanisms leading to altered stem cell function stem cell populations have to be studied directly. Until recently investigations of such nature in man were limited to hemopoietic progenitor populations that were committed to either granulopoiesis (CFU-C) [33] erythropoiesis (BFU-E) [18], or megakaryopoesis [25, 36]. A culture system for murine multilineage hemopoietic cells was first described by Metcalf et al. [32]. "Ihese primitive cells could be identified in culture by their ability to produce