Recent Developments in the Regulation of Peripheral Blood Stem Cell Mobilization and Engraftment by Cytokines, Chemokines, and Adhesion Molecules

Abstract

Peripheral blood stem cells (PBSC) have become the preferred source of stem cells for autologous transplantation because of the technical advantage and the shorter time to engraftment. Administration of hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) results in mobilization of PBSCs into the peripheral blood. G-CSF and GM-CSF differ somewhat in the number and composition of CD34(+) cells and effector cells mobilized to the peripheral blood; however, the molecular mechanism underlying the release and engraftment of CD34(+) cells by these growth factors is poorly understood. This review provides a recent update on the involvement of hematopoietic growth factors, chemokines, adhesion molecules, and chemokine receptors in the regulation of stem cell release and engraftment. The involvement of very late antigen-4 (VLA-4), VLA-5, leukocyte function associated-1 molecule (LFA-1), and L-selectin and their receptors CXCR4 and its ligand SDF-1 will be discussed, and cross talk between these factors will also be reviewed in the context of stem cell release and engraftment. Finally, PBSC mobilization by chemokines will be reviewed in relation to hematopoietic growth factors.

Acute Alcohol Intoxication Inhibits the Lineage-c-kit+Sca-1+ Cell Response to Escherichia Coli Bacteremia.

“…Both G-CSF and KC are potent factors mediating the bone marrow release of hematopoietic stem cells and progenitors in mice (29)(30)(31). In the present study, the plasma levels of these two cytokines were significantly increased following i.v.…”

“…These mediators are potent stimulants for inflammation, granulopoiesis, and mobilization of hematopoietic precursor cells from the bone marrow into the systemic circulation (29)(30)(31). Studies have shown that the number of hematopoietic precursor cells is increased in the systemic circulation in hosts challenged with bacterial components (32).…”

Mobilization of Myeloma Cells Involves SDF‐1/CXCR4 Signaling and Downregulation of VLA‐4

“…It has been shown that downregulation of adhesion molecules and disruption of CXCR4/SDF-1 signaling occurs during the process of HSC mobilization [9][10][11][12][13][14]. Similarly, it has been shown that circulating cancer cells exhibit reduced expression of adhesion molecules and CXCR4, and upregulation of CXCR4 and adhesion molecules were detected in metastatic cancer cells [26-36, 39-42, 44-46].…”

“…The molecular events and signaling molecules involved in HSC mobilization have been extensively studied. Thus, downregulation of adhesion molecules and desensitization of the CXCR4/stromal cell-derived factor (SDF-1) chemotaxis are critical events in growth factor-induced and/or chemotherapy-induced mobilization of HSC [9][10][11][12][13][14].…”

Cytokine control of developmental programs in normal hematopoiesis and leukemia

“…This ability to repopulate lethally irradiated hosts is the basis for bone marrow transplantation. The ®nding that G-CSF and GM-CSF can induce the migration of HSCs from the bone marrow to the peripheral blood (reviewed in Gazitt, 2001), has simpli®ed the procedure for stem cell harvesting for transplantation. This shows that like the hematopoietic in vitro colony forming cells, HSCs also respond to CSFs and both types of cells are induced to migrate to the peripheral blood by G-CSF and GM-CSF (Horsfall et al, 2000;Gazitt, 2001).…”