Stem Cell Homing

Homing was initially described as a process that orchestrates the migration of posttransplantation hematopoietic stem cells (HSCs) from peripheral blood to the bone marrow microenvironment, where these cells settle into specific stem cell niches. Thus homing of HSCs to their niches precedes engraftment and the establishment of transplant-derived hematopoiesis. Homing can also be understood more broadly as the migration of non-HSC-specific areas in tissues. It is enforced by chemotactic factors released in a given microenvironment that attract migrating cells. These chemotactic factors may by peptide-based (eg, chemokines or growth factors), bioactive phosphosphingolipids [eg, sphingosine-1-phosphate (S1P) or ceramide-1-phosphate (C1P)], or extracellular nucleotides (eg, ATP or UTP). Stem cells may also respond to a Ca2+ or H+ gradient by employing calcium- or proton-sensing receptors, respectively. Homing may also be sensitized by certain factors, such as small antimicrobial cationic peptides (eg, LL-37 or β2-defensin), or modulated by certain pharmacological compounds that affect cholesterol-enriched membrane lipid raft formation.