Pluripotent Stem Cells Do Not Completely Maintain Normal Human Steady‐State Haemopoiesis

Since the classical work on the regulation of canine erythropoiesis by Alpen & Cranmore (1959), it has been generally accepted that recognizable bone‐marrow cells are continuously replaced from sources of unrecognizable precursors. Although many features of pluripotent stem cells (PSC) and committed haemopoietic precursors have been determined, direct demonstration of a continuous influx, under normal steady‐state conditions, from PSC into the recognizable bone‐marrow cell compartments is still lacking. There is abundant evidence that PSC, in a number of species, including primates, resemble atypical or immature (‘transitional’) lumphocytes. By utilizing the technique of quantitative 14 C‐autoradiography, we have measured the activities of DNA and protein synthesis in individual bone‐marrow cells of two healthy humans. A positive relationship was established between the protein synthesis rate and rate of movement through the cell cycle in all proliferative compartments. Lymphoid cells, considered to contain the fraction of PSC, were found in the lower range of this relationship. These low metabolic rates exclude fast growth as well as short cell‐cycle times. In view of the low frequency of the potential PSC in the human bone marrow, amounting to less than 2%, these cells cannot be considered to represent a source continuously supplying the pool of rapidly proliferating, recognizable blast cells in the bone marrow under steady‐state conditions. Some self‐maintenance of a subcompartment within the pool of recognizable normal bone‐marrow blast cells is therefore suggested.