marrowhoming

Marrow homing, also referred to as bone marrow homing, is the process by which hematopoietic stem and progenitor cells (HSPCs) migrate from the bloodstream and engraft in the bone marrow after transplantation or mobilization. Efficient homing is a prerequisite for successful engraftment and long-term hematopoietic reconstitution.

The movement of HSPCs to the marrow is guided by a network of signals and adhesion interactions. A central mechanism involves the chemokine CXCL12, also known as SDF-1, produced by bone marrow stromal and endothelial cells, which creates a directed gradient sensed by CXCR4 receptors on HSPCs. Adhesion molecules, including VLA-4 (integrin α4β1) and its ligand VCAM-1, mediate tethering and stable lodging on marrow endothelium, while selectins and other adhesion receptors support rolling and transmigration into the niche. Matrix remodeling enzymes and signals from the bone marrow microenvironment facilitate entry into the perivascular and endosteal niches where HSPCs reside. Endothelial and niche cells, such as osteoblasts and mesenchymal stromal cells, provide cues that promote retention and quiescence or expansion of engrafted cells.

Clinical relevance is greatest in hematopoietic stem cell transplantation, where effective marrow homing correlates with faster neutrophil and platelet recovery and overall engraftment success. Factors influencing homing include cell dose, donor and recipient characteristics, conditioning regimens, and the inflammatory milieu. Strategies to enhance homing in clinical settings include ex vivo priming of HSPCs with prostaglandin E2, glycoengineering to increase selectin-ligand interactions (fucosylation), and optimized mobilization protocols. Research continues to refine understanding of the niche signals that optimize engraftment and to develop methods for real-time assessment of homing efficiency.