Hematopoietic Stem Cells: Uncomfortable Considerations.

Purpose: This report defines new concepts of hematopoietic stem cell biology.

Recent findings: We have utilized 3 different approaches which show that long-term repopulating hematopoietic stem cells are actively cycling and always changing phenotype. In addition this is reversible. This indicates that the stem cell cannot be purified by current epitope selection approaches. The vast bulk of hematopoietic stem cells are discarded in different populations when stem cells are purified to lineage negative c-kit positive and Sca-1 positive cells. Studies to define the hematopoietic niche have been largely carried out on these irrelevant purified cells and thus are not definitive. Studies have indicated the presence of baseline stem cells which function during the normal lifetime of mice. Baseline hematopoiesis appears to be run by thousands of relatively short lived clones with limited differentiation capacity. Thus there appear to be two basic hematopoietic stem cell modes; emergency and baseline.