Stem cell homing and repopulation are not well understood. The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 were found to be critical for murine bone marrow engraftment by human severe combined immunodeficient (SCID) repopulating stem cells. Treatment of human cells with antibodies to CXCR4 prevented engraftment. In vitro CXCR4-dependent migration to SDF-1 of CD34+CD38-/low cells correlated with in vivo engraftment and stem cell function. Stem cell factor and interleukin-6 induced CXCR4 expression on CD34+ cells, which potentiated migration to SDF-1 and engraftment in primary and secondary transplanted mice. Thus, up-regulation of CXCR4 expression may be useful for improving engraftment of repopulating stem cells in clinical transplantation.
"It was hypothesized that the delivery of molecules which regulates the microenvironment in the brain infarct can increase the degree and duration of neurogenesis and angiogenesis after stroke. Among the milieu of chemicals expressed in the injured microenvironment , stromal cell-derived factor-1a (SDF-1a or CXCL12a) and its unique receptor chemokine CXC motif receptor (CXCR4) is a candidate molecule that modulates the microenvironment in the infarcted brain  . SDF-1a is a major chemoattractant molecule for neural stem cells (NSCs), endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), and is recognized as a prime candidate in neurorestorative interventions. "
"Dysregulation of stromal components of the HP niches within the BM, such as changes in the levels of chemokines from osteoblasts (Obs) and other mesenchymal cells, has been associated with HP egress (Ding and Morrison, 2013; Greenbaum et al., 2013; Mé ndez-Ferrer et al., 2010; Omatsu et al., 2010; Petit et al., 2002; Sugiyama et al., 2006; Visnjic et al., 2004). Specifically, the deletion of the major hematopoietic stem cell and progenitor (HSC/P) traffic regulator Cxcl12 (Peled et al., 1999, 2000) from Cxcl12-abundant reticular cells and Ob results in constitutive HP mobilization and a loss of B-lymphoid progenitors, whereas their HSC function is normal (Greenbaum et al., 2013). Physiological regulation of these mesenchymal components modulates HP trafficking and is afforded by several mechanisms, including signals derived from BM-resident macrophages (MFs) (Casanova-Acebes et al., 2013; Chow et al., 2011; Christopher et al., 2011; Winkler et al., 2010). "
[Show abstract][Hide abstract] ABSTRACT: In the bone marrow (BM), hematopoietic progenitors (HPs) reside in specific anatomical niches near osteoblasts (Obs), macrophages (MΦs), and other cells forming the BM microenvironment. A connection between immunosurveillance and traffic of HP has been demonstrated, but the regulatory signals that instruct the immune regulation of HP circulation are unknown. We discovered that the BM microenvironment deficiency of p62, an autophagy regulator and signal organizer, results in loss of autophagic repression of macrophage contact-dependent activation of Ob NF-κB signaling. Consequently, Ob p62-deficient mice lose bone, Ob Ccl4 expression, and HP chemotaxis toward Cxcl12, resulting in egress of short-term hematopoietic stem cells and myeloid progenitors. Finally, Ccl4 expression and myeloid progenitor egress are reversed by deficiency of the p62 PB1-binding partner Nbr1. A functional "MΦ-Ob niche" is required for myeloid progenitor/short-term stem cell retention, in which Ob p62 is required to maintain NF-κB signaling repression, osteogenesis, and BM progenitor retention.
"PKCζ induces motility, adhesion and survival of CD34+ cells and MMP-2, and MMP-9 secretion. In addition, CXCR4 expression is dependent on stem cell factor (SCF) . SDF-1 is the most powerful HSC chemoattractant and survival regulator. "
[Show abstract][Hide abstract] ABSTRACT: Following chemotherapy and/or the administration of growth factors, such as granulocyte-colony stimulated factor (G-CSF), hematopoietic stem cells (HSC) mobilize from bone marrow to peripheral blood. This review aims to systematically present the structure of the HSC "niche" and elucidate the mechanisms of their mobilization. However, this field is constantly evolving and new pathways and molecules have been shown to contribute to the mobilization process. Understanding the importance and the possible primary pathophysiologic role of each pathway is rather difficult, since they share various overlapping components. The primary initiating event for the mobilization of HSC is chemotherapy-induced endogenous G-CSF production or exogenous G-CSF administration. G-CSF induces proliferation and expansion of the myelomonocytic series, which leads to proteolytic enzyme activation. These enzymes result in disruption of various receptor-ligand bonds, which leads to the disanchorage of HSC from the bone marrow stroma. In everyday clinical practice, CXC chemokine receptor-4 (CXCR4) antagonists are now being used as mobilization agents in order to improve HSC collection. Furthermore, based on the proposed mechanisms of HSC mobilization, novel mobilizing agents have been developed and are currently evaluated in preclinical and clinical studies.
BioMed Research International 08/2014; 2014:835138. DOI:10.1155/2014/835138 · 3.17 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.