Stem Cell Homing: From Physiology to Therapeutics

Steps in hematopoietic stem cell (HSC) homing and egress to and from marrow. Homing (left hand panel) occurs in the marrow sinusoidal endothelium. (1) Selectin ‐mediated braking or rolling occurs. Selectins involved include P‐selectin which interacts with CD162, SLex, and E‐selectin which recognizes CD15, SLex, and CD162 on stem cells. (2) HSCs migrate on adhesion ligands presented by the vascular endothelium, so‐called tethering. This involves CD4 9d‐f, CD11b, and CD11c on the hematopoietic stem and progenitor cells and CD106/fibronectin, laminin, and ICAM‐1 on endothelium as well as numerous other adhesion receptors and their ligands. (3) Changes in integrin conformation facilitate tight adhesion to the endothelial cell. (4) The stem cel l then migrates through the endothelial cell cytoplasm or paracellularly. The cell will then migrate through matrix to reach the lodging destination. This is facilitated by CXCL12,c ‐kit ligand, cathepsins, and matrix metalloproteinases. Egress (right hand panel) involves: (1) Matrix transmigration in response to chemokine and growth factor effects. Matrix components involved include collagen IV, laminin, fibronectin, hyaluronic acid, and tenascin; among others. (2) Trans ‐endothelial migration, and (3) Cell release with disruption of receptor/ligand interactions such as those between between CXCL12 and CXCR4 or CD49d and CD106 (VCAM‐1). AbstractStem cell homing is a multi ‐step endogenous physiologic process which is al...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Translational and Clinical Research Source Type: research