Trafficking and Homing of Hematopoietic Stem Cells

Migration of Stem Cells

The ability of hematopoietic stem cells to circulate and migrate from marrow to blood and back is an aspect of the hematopoietic system that has been conserved through evolution. Although the biologic role and physiologic significance of this constitutive hematopoietic stem cells circulation remains unclear, it is this capacity to traffic that leads to hematopoietic cell reconstitution and forms the essential requirement for success of hematopoietic cell Transplantation in the treatment of hematologic and nonhematologic diseases.

Restoration of normal blood cell count after Stem Cells Transplantation

The restoration of adequate blood cell production after transplantation requires a series of balanced interactions between the infused hematopoietic stem cells and its complex supporting marrow microenvironment. The initial step requires infused hematopoietic stem cells to adhere to the marrow endothelium with sufficient strength to overcome the shear forces of blood flow.

Mechanism of adhesion of transplanted stem cells

The dominant hematopoietic stem cell surface molecules that mediate adhesion and arrest are the selectin ligands P-selectin glycoprotein ligand-1, and the hematopoietic cell L- and E-selectin ligands that interact principally with endothelial E-selectin. Other hematopoietic stem cells surface adhesion molecules that mediate adherence to the marrow endothelium are a subset of the integrin superfamily, principally very late antigen-4, and lymphocyte function antigen-1, that interact with endothelial immunoglobulin (Ig) superfamily receptors (e.g., vascular cell adhesion molecule [VCAM]-1), and the hyaluronate receptor CD44 .HSCs that are null for the integrins cannot migrate to their marrow niche even though they proliferate and differentiate in the fetal liver.

Following firm adherence, the transendothelial movement and intraparenchymal homing to hematopoietic niches located within the inner endosteal surface of the bone are predominantly regulated by a gradient of extracellular matrix bound stromal cell-derived factor-1 (also known as CXCL12) binding to the chemokine-related receptor (CXCR4) on hematopoietic stem cells.

The requirement for CXCR4 expression on hematopoietic stem cells for homing and engraftment is well documented and forms the basis for new agents that help mobilize marrow stem cells for clinical use. Mice deficient in CXCR4 develop fetal liver hematopoiesis but die prenatally as a consequence of the lack of marrow hematopoiesis. Following successful homing, the initial adhesion of the hematopoietic stem cell within the hematopoietic niche appears regulated at least in part by annexin II as inhibitors reduce binding to the marrow microenvironment.