Mobilization and homing of hematopoietic stem cells

Hematopoietic stem cells (HSC) are a population of precursor cells that posses the capacity for self-renewal and multilineage differentiation. In the bone marrow (BM), HSCs warrant blood cell homeostasis, but at the same time a stable pool of functional cells must be constantly maintained. For this, HSCs constitute a model in which subpopulations of quiescent and active adult stem cells co-exist in the same tissue, in specific microenvironment called stem-cell "niches." These microenvironments keep the stem cells at quiescent (osteoblastic niche) for its self-renewal and activate the stem cells (vascular niche) for proliferation and/or injury repair, maintaining a dynamic balance between self-renewal and differentiation. HSC reside in the bone marrow but can be forces into the blood, a process termed mobilization used clinically to harvest large number of cells for transplantation. At the same time, homing to the BM is necessary to optimize cell engraftment. Here, we summarize current understanding of HSC niche characteristics, and the physiological and pathological mechanisms that guide HSC mobilization both within the BM and to distant niches in the periphery. Mobilization and Homing are mirror process depending on an interplay between chemokines, chemokine receptors, intracellular signaling, adhesion moleculas and proteases. The interaction between SDF-1/CXCL12 and its receptor CXCR4 is critical to retain HSCs within the bone marrow. Current mobilization strategies used in clinic, mainly G-CSF cytokine, are well tolerated but often produce suboptimal number of collected HSCs. Novel agents (AMD3100, stem cell factor, GROßT.) are being developed to enhance the mobilization to modify the signaling into the niche and boost the stem cell harvest, increasing the number of HSCs available for the transplant.