Enhancing the migration and engraftment of human and mouse long-term hematopoietic stem cells

Abstract

For over 50 years, bone marrow transplants have used CD34 to select stem cells. Recent research suggests that the most primitive hematopoietic stem cells (HSCs), long-term HSCs (LT-HSCs), are found in the CD34-negative portion of murine and human bone marrow cells. LT-HSCs are rare and cannot be isolated directly, making them difficult to study. During a bone marrow transplant, these stem cells must find their way to the bone marrow niche and engraft to become blood cells. Several cell adhesion molecules on the stem cell engage with their ligands on the endothelial cells lining the bone marrow vasculature to control this migration. Human LT-HSCs cells do not migrate and engraft well when infused in vivo, which may be due to a lack of adhesion molecules. Thus, the goal of this study was to determine whether this population of HSCs lacked adhesion systems (proteins and carbohydrate modifications) and, if so, to improve their migration and engraft ability by modifying key mechanistic steps in the adhesion cascade. Therefore, we investigated how distinct hematopoietic stem cell populations migrate to the bone marrow using adhesion mechanisms. This study represents the first direct analysis of adhesion molecules expression in LT-HSC and will potentially shed light on methods to optimally use these very valuable cells in the clinical bone marrow and cord blood transplants worldwide.