Plasma elevation of stromal cell–derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells

Hattori, Koichi; Heissig, Beate; Tashiro, Kei; Honjo, Tasuku; Tateno, Masatoshi; Shieh, Jae‐Hung; Hackett, Neil R.; Quitoriano, Mannix S.; Crystal, Ronald G.; Rafii, Shahin; Moore, Malcolm A.S.

doi:10.1182/blood.v97.11.3354

Cited by 483 publications

(345 citation statements)

References 31 publications

Supporting

Mentioning

323

Contrasting

Unclassified

Order By: Relevance

“…These increases were not specific to this myeloproliferative disorder as high levels of SDF-1 were also observed in the plasma of patients with PV ( Figure 6). The elevation of SDF-1 observed in the blood of the animal model and of the PMF patients were modest (~2-4-fold) (Figure 2 and 6) when compared to the levels required to experimentally induce stem/progenitor cell mobilization in NOD/SCID mice (25-fold) 34,35 and are, therefore, unlikely to be responsible for a gradient driven mobilization of stem/progenitor cells.…”

Section: Discussionmentioning

confidence: 90%

“…The concentration of soluble SDF-1 in the blood, however, increases in association with many of the conditions that induce stem/progenitor cell mobilization. Both sustained elevations of SDF-1 in NOD/SCID mice delivered by an adenoviral vector delivery system [34][35][36] , and chronic administration to the animals of SDF-1 peptide analogs 37,38 , result in mobilization of stem/ progenitor cells. In addition, increased plasma SDF-1 levels are also observed during mobilization induced by sulfated glycans 39 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Altered SDF-1/CXCR4 axis in patients with primary myelofibrosis and in the Gata1low mouse model of the disease

Migliaccio

Martelli

Verrucci

et al. 2008

Experimental Hematology

View full text Add to dashboard Cite

Objective-To assess whether alterations in the SDF-1/CXCR4 occur in patients with primary myelofibrosis (PMF) and in Gata1 low mice, an animal model for myelofibrosis, and whether these abnormalities might account for increased stem/progenitor cell trafficking.Materials and Methods-In the mouse, SDF-1 mRNA levels were assayed in liver, spleen and marrow. SDF-1 protein levels were quantified in plasma and marrow and CXCR4 mRNA and protein levels were evaluated on stem/progenitor cells and megakaryocytes purified from the marrow. SDF-1 protein levels were also evaluated in plasma and in marrow biopsy specimens obtained from normal donors and PMF patients.Results-In Gata1 low mice, the plasma SDF-1 protein was 5-times higher than normal in younger animals. Furthermore, SDF-1 immuno-staining of marrow sections progressively increased with age. Similar abnormalities were observed in PMF patients. In fact, the plasma SDF-1 levels in PMF patients were significantly higher (by 2-fold) than normal (p<0.01) and SDF-1 immuno-staining of marrow biopsiy specimens demonstrated increased SDF-1 deposition in specific areas. In two of the patients, SDF-1 deposition was normalized by curative therapy with allogenic stem cell transplantation. Similarly to what already has been reported for PMF patients, the marrow from Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Gata1 low mice contained fewer CXCR4 pos CD117 pos cells and these cells expressed low levels of CXCR4 mRNA and protein. NIH Public AccessConclusion-Similar abnormalities in the SDF-1/CXCR4 axis are observed in PMF patients and in the Gata1 low mice model of myelofibrosis. We suggest that these abnormalities contribute to the increased stem/progenitor cell trafficking observed in this mouse model as well as patients with PMF.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Altered SDF-1/CXCR4 axis in patients with primary myelofibrosis and in the Gata1low mouse model of the disease

Migliaccio

Martelli

Verrucci

et al. 2008

Experimental Hematology

View full text Add to dashboard Cite

show abstract

“…12 On the other hand, it has been demonstrated that the higher concentration of CXCL12 in the peripheral circulation facilitates the mobilization of CD34 cells in mice. Hattori et al 18 have reported that the overexpression of CXCL12 in the peripheral circulation (for example, the i.v. injection of an recombinant adenovirus expressing CXCL12) results in the mobilization of haematopoietic cells with repopulating capacity, progenitor cells and precursor cells.…”

Section: Discussionmentioning

confidence: 99%

The CXCL12-3′A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation

Bogunia‐Kubik

Gieryng

Dłubek

et al. 2009

Bone Marrow Transplant

View full text Add to dashboard Cite

The interaction between CXCL12 and its receptor CXCR4 plays a crucial role in the homing and mobilization of haematopoietic progenitors. We investigated the putative association between a CXCL12 gene polymorphism, the G-A transition at position 801 in the 3 0 -untranslated region (3 0 UTR), and the yield of CD34 þ progenitors in 65 healthy allogeneic transplant donors who received G-CSF. Importantly, in this setting, the analysis was not biased by background disease or chemotherapy. The 3 0 UTR CXCL12 G801A polymorphism was detected using a PCR-RFLP technique with the MspI restriction enzyme and the frequency of CD34 þ progenitors was assessed by flow cytometry. The frequency as well as the number of CD34 þ progenitor cells in the first leukapheresis product was significantly higher from donors with the CXCL12-3 0 A allele compared to GG homozygotes (Po0.05 in both cases), especially for subjects with the CXCL12-3 0 AA homozygous genotype (Po0.01 in both cases). Moreover, more leukaphereses were needed to obtain the required number of CD34 þ progenitors for transplantation from CXCL12-3 0 GG homozygous donors compared to the CXCL12-3 0 A carriers (P ¼ 0.003). In conclusion, the CXCL12-3 0 A allele was associated with a higher yield of CD34 þ cells from healthy donors of PBPC for allogeneic haematopoietic SCT.

show abstract

“…Direct evidence for the role of SDF-1 in regulating mobilization of pro-angiogenic BM cells in vivo has been demonstrated by plasma elevation of SDF-1, which stimulates mobilization of CXCR4 + BM cells, including HSCs and EPCs [31,32]. Increased elevation of SDF-1 concentration in the blood has been observed in ischemic models, while its concentration in the BM was decreased, thereby resulting in the mobilization of the pro-angiogenic cells [14,18,33].…”

Section: Sdf-1 Is the Primary Chemokine That Supports Mobilization Ofmentioning

confidence: 99%

The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis

Petit

Jin

Rafii

2007

Trends in Immunology

Self Cite

526

382

View full text Add to dashboard Cite

Pro-angiogenic bone marrow (BM) cells include subsets of hematopoietic cells that provide vascular support and endothelial progenitor cells (EPCs), which under certain permissive conditions could differentiate into functional vascular cells. Recent evidence demonstrates that the chemokine stromal-cell derived factor-1 (SDF-1, also known as CXCL12) has a major role in the recruitment and retention of CXCR4 + BM cells to the neo-angiogenic niches supporting revascularization of ischemic tissue and tumor growth. However, the precise mechanism by which activation of CXCR4 modulates neo-angiogenesis is not clear. SDF-1 not only promotes revascularization by engaging with CXCR4 expressed on the vascular cells but also supports mobilization of pro-angiogenic CXCR4 + VEGFR1 + hematopoietic cells, thereby accelerating revascularization of ischemic organs. Here, we attempt to define the multiple functions of the SDF-1-CXCR4 signaling pathway in the regulation of neo-vascularization during acute ischemia and tumor growth. In particular, we introduce the concept that, by modulating plasma SDF-1 levels, the CXCR4 antagonist AMD3100 acutely promotes, while chronic AMD3100 treatment inhibits, mobilization of pro-angiogenic cells. We will also discuss strategies to modulate the mobilization of essential subsets of BM cells that participate in neo-angiogenesis, setting up the stage for enhancing revascularization or targeting tumor vessels by exploiting CXCR4 agonists and antagonists, respectively.

show abstract

Plasma elevation of stromal cell–derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells

Cited by 483 publications

References 31 publications

Altered SDF-1/CXCR4 axis in patients with primary myelofibrosis and in the Gata1low mouse model of the disease

Altered SDF-1/CXCR4 axis in patients with primary myelofibrosis and in the Gata1low mouse model of the disease

The CXCL12-3′A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation

The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis

Contact Info

Product

Resources

About