Limited Proliferative Potential of Primitive Hematopoietic Stem Cells: Hematopoiesis by Clonal Succession

Abstract

The hierarchy of hematopoietic stem cells (HSC) is represented by several categories of maturating pluripotent pro-genitors. 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 +/+ hematopoietic cells to cure anemia of W-mutant mice has been also used for the determination of PHSC [4–6].