Human Hematopoietic Stem Cells: The Current Understanding and Future Prospects

Abstract

 Based on the recent progress of fluorescence-activated cell sorting technology, murine hematopoietic stem cells (HSCs) can be purified to the single cell level. The immunophenotype of murine HSCs is CD34^low/−c-kit⁺Sca-1⁺Lin⁻ (CD34^low/− KSL). However, the stem cell nature of primitive human HSCs has not been fully elucidated. The biology of human HSCs is a current topic of interest that has important implications for hematopoietic stem cell transplantation (HSCT) as well as basic research on HSCs. We identified human cord blood (CB) -derived CD34⁻ SCID-repopulating cells (SRCs) (HSCs), which seemed to be a counterpart of murine CD34^low/− KSL cells, using an intra-bone marrow injection (IBMI) method. Our series of studies has elucidated the stem cell nature of these CD34⁻ HSCs as well as CD34⁺ HSCs. The purpose of this review is to provide an update of the concept of the immunophenotype and functional characteristics of human primitive CD34^+/− HSCs. In addition, the significance of the application of the IBMI technique in clinical HSCT is also discussed. Recent advances in the understanding of the biological nature of human HSCs may make it possible to fully characterize the most primitive class of human HSCs, and thereby clarify the human HSC hierarchy, in the near future.