Limited proliferative potential of primitive hematopoietic stem cells: hematopoiesis by clonal succession.

The hierarchy of hematopoietic stem cells (HSC) is represented by several categories of maturating pluripotent progenitors. Most of them are the members of transitional cell populations and, obviously, have no capacity for self-maintenance, i. e., are not capable of giving rise to self-replicating offspring with the same proliferative potential as the parent had [1]. The foundator of this hierarchy has not yet been identified. The most probable candidate at present is the cells supporting long-term hematopoiesis in vivo after repopulation of lethally irradiated or genetically defective W -mutant mice or in vitro in long-term culture. However, the self-renewal is also not proven for these cells, and hematopoiesis, at least in culture, occurs by clonal succession [2]. The experimental data support the hypothesis that even primitive HSC (PHSC) exhibit high, though limited, proliferative potential. This cell category is usually identified by competitive repopulation assay using a mixture of tested and standard cells identifiable by biochemical, immunological, karyological, or other markers [3]. Limiting dilution analysis based on the ability of small numbers of + I + hematopoietic cells to cure anemia of W -mutant mice has been also used for the determination of PHSC [4-6]. In the present study, the characteristics of PHSC were investigated in long-term bone marrow culture by both competi-