Hematopoietic Stem Cells
It is now known that Hematopoietic Stem Cells (HSCs) progress through defined stages of maturation that result in gradual loss of multi-lineage potential, and commitment to various blood cell phenotypes. Mouse HSCs were first isolated as part of the bone marrow fraction depleted of lineage positive cells. Subsequently, it was discovered that the lineage-negative fraction could be significantly enriched for HSCs by further selecting the lin-Sca-1+c-Kit+ (LSK) population of bone marrow. In 2005, it was demonstrated by Morrison et al that a combination of the SLAM family of proteins could also be used to efficiently identify and isolate HSCs. They found the CD150+CD48-CD244-CD41- fraction of mouse bone marrow to be significantly enriched for long-term reconstituting ability. In humans, the isolation of a lin-CD34+CD90+ progenitor cell resulted in the purification of a homogeneous HSC population. The critical test for HSCs is in their ability to clinically rescue myelo-ablated hosts from hematopoietic failure, and establish long-term multi-hematopoietic lineage reconstitution.