CXCR4 signaling in the regulation of stem cell migration and development

Abstract

The regulated migration of stem cells is a feature of the development of all tissues and also of a number of pathologies. In the former situation the migration of stem cells over large distances is required for the correct formation of the embryo. In addition, stem cells are deposited in niche like regions in adult tissues where they can be called upon for tissue regeneration and repair. The migration of cancer stem cells is a feature of the metastatic nature of this disease. In this article we discuss observations that have demonstrated the important role of chemokine signaling in the regulation of stem cell migration in both normal and pathological situations. It has been demonstrated that the chemokine receptor CXCR4 is expressed in numerous types of embryonic and adult stem cells and the chemokine SDF-1/CXCL12 has chemoattractant effects on these cells. Animals in which SDF-1/CXCR4 signaling has been interrupted exhibit numerous phenotypes that can be explained as resulting from inhibition of SDF-1 mediated chemoattraction of stem cells. Hence, CXCR4 signaling is a key element in understanding the functions of stem cells in normal development and in diverse pathological situations.

Adult Stem Cell Mobilization Enhances Intramembranous Bone Regeneration: A Pilot Study

“…This new paradigm uses pharmacologic induction of mobilization and endogenous mechanisms of cell homing and engraftment to sites of injury. It is plausible this strategy simply mimics and amplifies normal repair mechanisms as progenitor cells are mobilized to the PB after stroke [41], vascular trauma [20], musculoskeletal trauma [31,32], fracture [3,34], distraction osteogenesis [34], and myocardial infarction [60]. An important pathway for stem cell mobilization is the SDF-1/CXCR4 axis and there are recent data supporting the concept that transient disruption of this receptor-ligand complex through the CXCR4 antagonist, AMD3100, enhances bone formation in vivo [57,59].…”

CXCR4 Controls Ventral Migration of Sympathetic Precursor Cells

“…Since chemokines, a superfamily of small glycoproteins with chemoattractant ability, control multiple events during embryonic development including directed cell migration (Bagri et al, 2002;Tran et al, 2004;Belmadani et al, 2005;Miller et al, 2008;Raz and Mahabaleshwar, 2009), we sought to investigate their role in patterning the PNS. We show here with gain-and loss-offunction experiments, combined with intravital time-lapse imaging, that differential expression of CXCR4 and its ligand SDF-1 sculpt a common stream of migrating NCCs into two discrete structures, the SGs and DRGs.…”

CXCR7 Protein Is Not Expressed on Human or Mouse Leukocytes

“…This receptorligand pair has been implicated in a wide range of biological processes, including development, stem cell biology, angiogenesis, leukocyte trafficking, cancer, neurodegenerative disorders, inflammatory disorders, atherosclerosis, and HIV pathology (1)(2)(3)(4)(5)(6)(7)(8)(9). Until recently, CXCL12 and CXCR4 were thought to be exclusive partners-a relative rarity in the chemokine network.…”