Homing of Human Hematopoietic Stem and Progenitor Cells: New Insights, New Challenges?

In healthy adults, hematopoiesis takes place in the bone marrow, where the majority of hematopoietic progenitor cells (HPC) reside. In patients undergoing chemo- and/or radiotherapy, hematopoiesis is seriously disturbed. Reconstitution of bone-marrow function can be achieved by bone marrow transplantation or peripheral blood stem cell transplantation. The success of stem cell transplantation depends on the ability of intravenously infused stem cells to lodge in the bone marrow, a process referred to as homing. However, the molecular mechanisms that govern this process are poorly understood. It is hypothesized that homing is a multistep process, consisting of adhesion of the HPC to endothelial cells of the marrow sinusoids, followed by transendothelial migration directed by chemoattractants, and finally anchoring within the extravascular bone marrow spaces where proliferation and differentiation will occur. In this review, we discuss the factors that determine the engraftment potential of stem cells, and focus on various aspects of migration and homing of HPC, i.e., the role of the chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4, the involvement of adhesion molecules, and the induction of actin polymerization in the HPC. Defining the role of chemokines and adhesion molecules in human stem cell migration and engraftment will help us uncover the underlying mechanisms that regulate stem cell homing and will eventually advance clinical stem cell transplantation.