Circulating Bone Marrow-Derived Osteoblast Progenitor Cells Are Recruited to the Bone-Forming Site by the CXCR4/Stromal Cell-Derived Factor-1 Pathway

Stem Cells ◽  
2008 ◽  
Vol 26 (1) ◽  
pp. 223-234 ◽  
Author(s):  
Satoru Otsuru ◽  
Katsuto Tamai ◽  
Takehiko Yamazaki ◽  
Hideki Yoshikawa ◽  
Yasufumi Kaneda
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Osteoblast Progenitor ◽  
Stromal Cell Derived Factor

scholarly journals Transforming growth factor-β1 modulates responses of CD34+ cord blood cells to stromal cell-derived factor-1/CXCL12

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 485-493 ◽  
Author(s):  
Sunanda Basu ◽  
Hal E. Broxmeyer
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Cd34 Cells ◽  
Stromal Cell Derived Factor ◽  
Tgf Β1

Abstract Disruption of stromal cell-derived factor-1 (SDF-1/CXCL12 [CXC chemokine ligand 12]) interaction leads to mobilization of stem/progenitor cells from bone marrow to circulation. However, prolonged exposure of CD34+ cells to SDF-1 desensitizes them to SDF-1. So how do cells remain responsive to SDF-1 in vivo when they are continuously exposed to SDF-1? We hypothesized that one or more mechanisms mediated by cytokines exist that could modulate SDF-1 responsiveness of CD34+ cells and the desensitization process. We considered transforming growth factor-β1 (TGF-β1) a possible candidate, since TGF-β1 has effects on CD34+ cells and is produced by stromal cells, which provide niches for maintenance and proliferation of stem/progenitor cells. TGF-β1 significantly restored SDF-1–induced chemotaxis and sustained adhesion responses in cord blood CD34+ cells preexposed to SDF-1. Effects of TGF-β1 were dependent on the dose and duration of TGF-β1 pretreatment. Phosphorylation of extracellular signal-regulated kinase 1 (Erk1)/Erk2 was implicated in TGF-β1 modulation of migratory and adhesion responses to SDF-1. Our results indicate that low levels of TGF-β1 can modulate SDF-1 responsiveness of CD34+ cells and thus may facilitate SDF-1–mediated retention and nurturing of stem/progenitor cells in bone marrow.

scholarly journals Platelets secrete stromal cell–derived factor 1α and recruit bone marrow–derived progenitor cells to arterial thrombi in vivo

2006 ◽  
Vol 173 (3) ◽  
pp. i5-i5
Author(s):  
Steffen Massberg ◽  
Ildiko Konrad ◽  
Katrin Schürzinger ◽  
Michael Lorenz ◽  
Simon Schneider ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Stromal Cell Derived Factor

The Chemokine Receptor CXCR-4 Is Expressed on CD34+Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial Migration Induced by Stromal Cell-Derived Factor-1

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4523-4530 ◽  
Author(s):  
Robert Möhle ◽  
Frank Bautz ◽  
Shahin Rafii ◽  
Malcolm A.S. Moore ◽  
Wolfram Brugger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Leukemic Cell ◽  
Transendothelial Migration ◽  
Leukemic Cells ◽  
Hematopoietic Progenitor ◽  
Leukemic Cell Lines ◽  
Stromal Cell Derived Factor

Abstract The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 (fusin, LESTR) are likely to be involved in the trafficking of hematopoietic progenitor and stem cells, as suggested by the reduced bone marrow hematopoiesis in SDF-1–deficient mice and the chemotactic effect of SDF-1 on CD34+ progenitor cells. Migration of leukemic cells might also depend on the expression of chemokine receptors. Therefore, we analyzed expression of CXCR-4 on mobilized normal CD34+ progenitors and leukemic cells. In addition, SDF-1–induced transendothelial migration across a bone marrow endothelial cell layer was assessed in vitro. By flow cytometry, CXCR-4 was found to be expressed in significant amounts on circulating CD34+ hematopoietic progenitor cells, including more primitive subsets (CD34+/CD38− and CD34+/Thy-1+ cells). In accordance with the immunofluorescence data, CD34+ progenitors efficiently migrated across endothelium in response to SDF-1 containing conditioned medium from the stromal cell line MS-5. Leukemic blasts (mostly CD34+) from patients with acute myeloblastic leukemia (AML) expressed variable amounts of CXCR-4, which was functionally active, as demonstrated by a positive correlation between the SDF-1–induced transendothelial migration and the cell surface density of CXCR-4 (r = 0.97). Also recombinant SDF-1β induced migration of CXCR-4–positive leukemic blasts. The effect of both conditioned medium and recombinant SDF-1 was inhibited by a CXCR-4 blocking antibody. In contrast, CD34+ leukemic cell lines (KG1, KG1a, Kasumi-1, MOLM-1) expressed low levels or were negative for CXCR-4, and did not migrate. By reverse transcriptase-polymerase chain reaction (RT-PCR), however, basal levels of CXCR-4 mRNA were also detected in all leukemic cell lines. We conclude that CXCR-4 is expressed on CD34+cells including more primitive, pluripotent progenitors, and may therefore play a role in the homing of hematopoietic stem cells. CXCR-4 expressed in variable amounts on primary AML leukemic cells is functionally active and may be involved in the trafficking of malignant hematopoietic cells.

The Chemokine Receptor CXCR-4 Is Expressed on CD34+Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial Migration Induced by Stromal Cell-Derived Factor-1

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4523-4530 ◽  
Author(s):  
Robert Möhle ◽  
Frank Bautz ◽  
Shahin Rafii ◽  
Malcolm A.S. Moore ◽  
Wolfram Brugger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Leukemic Cell ◽  
Transendothelial Migration ◽  
Leukemic Cells ◽  
Hematopoietic Progenitor ◽  
Leukemic Cell Lines ◽  
Stromal Cell Derived Factor

The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 (fusin, LESTR) are likely to be involved in the trafficking of hematopoietic progenitor and stem cells, as suggested by the reduced bone marrow hematopoiesis in SDF-1–deficient mice and the chemotactic effect of SDF-1 on CD34+ progenitor cells. Migration of leukemic cells might also depend on the expression of chemokine receptors. Therefore, we analyzed expression of CXCR-4 on mobilized normal CD34+ progenitors and leukemic cells. In addition, SDF-1–induced transendothelial migration across a bone marrow endothelial cell layer was assessed in vitro. By flow cytometry, CXCR-4 was found to be expressed in significant amounts on circulating CD34+ hematopoietic progenitor cells, including more primitive subsets (CD34+/CD38− and CD34+/Thy-1+ cells). In accordance with the immunofluorescence data, CD34+ progenitors efficiently migrated across endothelium in response to SDF-1 containing conditioned medium from the stromal cell line MS-5. Leukemic blasts (mostly CD34+) from patients with acute myeloblastic leukemia (AML) expressed variable amounts of CXCR-4, which was functionally active, as demonstrated by a positive correlation between the SDF-1–induced transendothelial migration and the cell surface density of CXCR-4 (r = 0.97). Also recombinant SDF-1β induced migration of CXCR-4–positive leukemic blasts. The effect of both conditioned medium and recombinant SDF-1 was inhibited by a CXCR-4 blocking antibody. In contrast, CD34+ leukemic cell lines (KG1, KG1a, Kasumi-1, MOLM-1) expressed low levels or were negative for CXCR-4, and did not migrate. By reverse transcriptase-polymerase chain reaction (RT-PCR), however, basal levels of CXCR-4 mRNA were also detected in all leukemic cell lines. We conclude that CXCR-4 is expressed on CD34+cells including more primitive, pluripotent progenitors, and may therefore play a role in the homing of hematopoietic stem cells. CXCR-4 expressed in variable amounts on primary AML leukemic cells is functionally active and may be involved in the trafficking of malignant hematopoietic cells.

Chemokine stromal cell-derived factor-1α modulates VLA-4 integrin-dependent adhesion to fibronectin and VCAM-1 on bone marrow hematopoietic progenitor cells

2001 ◽  
Vol 29 (3) ◽  
pp. 345-355 ◽  
Author(s):  
Andrés Hidalgo ◽  
Francisco Sanz-Rodrı́guez ◽  
José Luis Rodrı́guez-Fernández ◽  
Beatriz Albella ◽  
Carolina Blaya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Stromal Cell Derived Factor

scholarly journals Enhanced c-Met activity promotes G-CSF–induced mobilization of hematopoietic progenitor cells via ROS signaling

Blood ◽  
2011 ◽  
Vol 117 (2) ◽  
pp. 419-428 ◽  
Author(s):  
Melania Tesio ◽  
Karin Golan ◽  
Simona Corso ◽  
Silvia Giordano ◽  
Amir Schajnovitz ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Reactive Oxygen ◽  
Target Of Rapamycin ◽  
Oxygen Species ◽  
Hematopoietic Progenitor ◽  
Stromal Cell Derived Factor

Abstract Mechanisms governing stress-induced hematopoietic progenitor cell mobilization are not fully deciphered. We report that during granulocyte colony-stimulating factor–induced mobilization c-Met expression and signaling are up-regulated on immature bone marrow progenitors. Interestingly, stromal cell–derived factor 1/CXC chemokine receptor-4 signaling induced hepatocyte growth factor production and c-Met activation. We found that c-Met inhibition reduced mobilization of both immature progenitors and the more primitive Sca-1+/c-Kit+/Lin− cells and interfered with their enhanced chemotactic migration to stromal cell–derived factor 1. c-Met activation resulted in cellular accumulation of reactive oxygen species by mammalian target of rapamycin inhibition of Forkhead Box, subclass O3a. Blockage of mammalian target of rapamycin inhibition or reactive oxygen species signaling impaired c-Met–mediated mobilization. Our data show dynamic c-Met expression and function in the bone marrow and show that enhanced c-Met signaling is crucial to facilitate stress-induced mobilization of progenitor cells as part of host defense and repair mechanisms.

Over-Expression of Stromal Cell-Derived Factor-1 in Non-Specialized Endothelium Enhances the Endothelium-Supported Transmigration, Maintenance, and Proliferation of Hematopoietic Progenitor Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2299-2299
Author(s):  
Jin-Hee Hwang ◽  
Seong-Woo Kim ◽  
Hwan-Jung Yun ◽  
Younghee Lee ◽  
Samyong Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Umbilical Vein ◽  
Cell Trafficking ◽  
Aberrant Expression ◽  
Hematopoietic Stem ◽  
Over Expression ◽  
Cd34 Cells ◽  
Stromal Cell Derived Factor

Abstract Stromal cell-derived factor-1 (SDF-1) plays a central role in the homing of hematopoietic stem cells and progenitor cells (HPCs) to bone marrow (BM). Tissue damage, most notably ischemia, induces the recruitment of bone marrow (BM)-derived stem/progenitor cells, which can lead to tissue repair. Moreover, damaged tissues and endothelium express and produce SDF-1. However, the effects of aberrant expression and production of SDF-1 in human endothelium on the biology of BM-derived stem/progenitor cells are not fully understood. To clarify this, we over-expressed the SDF-1 gene in human umbilical vein endothelial cells using an adenoviral vector (HUVEC/AdeSDF-1) and examined the transmigration, maintenance, and proliferation of HPCs supported by the endothelium. HUVEC/AdeSDF-1 monolayers induced the migration of MO7e cells and mobilized peripheral blood (mPB) CD34+ cells underneath the endothelium within a few hours, while HUVEC monolayers transfected with adenoviral vectors expressing LacZ (HUVEC/AdeLacZ) did not. A transmigration assay revealed that HUVEC/AdeSDF-1 monolayers supported the spontaneous transmigration of CD34+ cells to a greater degree than did HUVEC/LacZ monolayers (15 ± 4% vs. 5 ± 3%) and that transmigration was blocked with pretreatment of the input cells with pertussis toxin (PTX). The co-culturing of mPB CD34+ cells with HUVEC/AdeSDF-1 for up to 2 weeks led to a greater expansion of CD45+ cells and colony-forming cells, and reduced cell apoptosis. Furthermore, the co-culturing of mPB CD34+ cells with HUVEC/AdeSDF-1 led to the formation of numerous cobblestone areas, while mPB CD34+ cells plus HUVEC/AdeLacZ supported the formation of only a few cobblestone areas (253 ± 28 vs. 10 ± 3 per 2 x 104 mPB CD34+ cells at week-2), which were further enhanced by adding a combination of early-acting hematopoietic growth factors at low concentrations. To further elucidate whether SDF-1 is directly involved in the formation of cobblestone areas, mPB CD34+ cells were co-cultured with murine BM MS-5 stromal cells. Weekly PTX treatment, beginning 24 hours after start of co-culturing, markedly decreased the numbers of cobblestone areas by weeks 2 and 5, which indicates that SDF-1 is involved not only in the localization of primitive HPCs underneath the endothelium or BM stroma but also in the maintenance and proliferation of the cells. These results indicate that aberrant SDF-1 over-expression in any non-specialized endothelium induces BM-derived progenitor cell trafficking into extravasculr sites and promotes the maintenance and proliferation of the migrated cells.

scholarly journals FGF2 posttranscriptionally down-regulates expression of SDF1 in bone marrow stromal cells through FGFR1 IIIc

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1363-1372 ◽  
Author(s):  
Takayuki Nakayama ◽  
Noriko Mutsuga ◽  
Giovanna Tosato
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Stromal Cell ◽  
Marrow Stromal Cells ◽  
Hematopoietic Progenitor Cells ◽  
Pcr Analysis ◽  
Hematopoietic Progenitor ◽  
Stromal Cell Derived Factor

AbstractThe chemokine stromal cell–derived factor-1 (SDF-1) is constitutively expressed by bone marrow stromal cells and plays key roles in hematopoiesis. Fibroblast growth factor 2 (FGF2), a member of the FGF family that plays important roles in developmental morphogenic processes, is abnormally elevated in the bone marrow from patients with clonal myeloid disorders and other disorders where normal hematopoiesis is impaired. Here, we report that FGF2 reduces SDF-1 secretion and protein content in bone marrow stromal cells. By inhibiting SDF-1 production, FGF2 compromises stromal cell support of hematopoietic progenitor cells. Reverse-transcriptase–polymerase chain reaction (RT-PCR) analysis revealed that bone marrow stromal cells express 5 FGF receptors (FGFRs) among the 7 known FGFR subtypes. Blocking experiments identified FGFR1 IIIc as the receptor mediating FGF2 inhibition of SDF-1 expression in bone marrow stromal cells. Analysis of the mechanisms underlying FGF2 inhibition of SDF-1 production in bone marrow stromal cells revealed that FGF2 reduces the SDF-1 mRNA content by posttranscriptionally accelerating SDF-1 mRNA decay. Thus, we identify FGF2 as an inhibitor of SDF-1 production in bone marrow stromal cells and a regulator of stromal cell supportive functions for hematopoietic progenitor cells.

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