Vascular Endothelial Growth Factor and Angiopoietin-1 Stimulate Postnatal Hematopoiesis by Recruitment of Vasculogenic and Hematopoietic Stem Cells
By K. Hattori, S. Dias, B. Heissig, N. Hackett, D. Lyden, M. Tateno, D. Hicklin, Zhen-ping Zhu, L. Witte, R. Crystal and 2 more. Journal of Experimental Medicine, 2001
730 citations recorded by the source corpus.
Tyrosine kinase receptors for angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) are expressed not only by endothelial cells but also by subsets of hematopoietic stem cells (HSCs). To further define their role in the regulation of postnatal hematopoiesis and vasculogenesis, VEGF and Ang-1 plasma levels were elevated by injecting recombinant protein or adenoviral vectors expressing soluble VEGF165, matrix-bound VEGF189, or Ang-1 into mice. VEGF165, but not VEGF189, induced a rapid mobilization of HSCs and VEGF receptor (VEGFR)2+ circulating endothelial precursor cells (CEPs). In contrast, Ang-1 induced delayed mobilization of CEPs and HSCs. Combined sustained elevation of Ang-1 and VEGF165 was associated with an induction of hematopoiesis and increased marrow cellularity followed by proliferation of capillaries and expansion of sinusoidal space. Concomitant to this vascular remodeling, there was a transient depletion of hematopoietic activity in the marrow, which was compensated by an increase in mobilization and recruitment of HSCs and CEPs to the spleen resulting in splenomegaly. Neutralizing monoclonal antibody to VEGFR2 completely inhibited VEGF165, but not Ang-1–induced mobilization and splenomegaly. These data suggest that temporal and regional activation of VEGF/VEGFR2 and Ang-1/Tie-2 signaling pathways are critical for mobilization and recruitment of HSCs and CEPs and may play a role in the physiology of postnatal angiogenesis and hematopoiesis.
Subfields: Cell Biology, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/072f8cc791cf0e36f9edde42df3b7056ece1b16f
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cell Biology
In Molecular Biology
In Oncology
Citations in the corpus
- Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. (2007, background): “natal BM when systemically delivered (Hattori et al., 2001), and we have observed that BMSC-directed patterning and remodeling of pseudovascular structures in vitro is altered”
- Vascular Endothelial Growth Factor and Angiogenesis (2004, background): “Hattori et al. (2001) showed that high plasma levels of VEGF promoted the mobilization of EPCs through activation of metalloproteinases, adhesion molecules, and remodeling of the extracellular matrix within the bone marrow.”
- Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration (2003, background): “However, the angiogenic switch promotes mobilization of bone marrow–derived EPC”
- Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? (2002, background): “cgi?l=4254">sKitL ), which promotes haematopoietic-cell proliferation and motilit”
- Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. (2004, methodology): “Circulating VEGFR-2 /CD11b cells have previously been shown to represent an EPC population.(16,25) Quantitative analysis was performed on a FACStar flow cytometer (BD Biosciences).”
- Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1+ stem cells from bone-marrow microenvironment (2002, background): “We showed that VEGF-A and/or angiopoietin-1 mobilize BM-repopulating cell”
- Tumor microenvironment: The role of the tumor stroma in cancer (2007, background): “…and tumor induction in skin cancer models [Coussens et al., 2000; Crivellato and Ribatti, 2005], while eosinophils, associated with a host of solid tumors including colon, cervical, lung, breast, and ovary aswell as some lymphomas, can influence angiogenesis via VEGF production.”
- HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. (2008, background): “While VEGF is an important factor for the activation of MMP-9 in the bone marrow and subsequent mobilization of vascular progenitor cells (Hattori et al., 2001), SDF1a may be crucial for retaining CD45+ populations within the tumor ( Grunewald et al., 2006 )( Petit et al., 2007).”
- Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. (2005, background): “VEGF is one of several factors that can induce endothelial progenitor cell recruitment to the peripheral circulation ( 25 ).”
- Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. (2002, methodology): “…E3-deficient (E1a E3 E4 ) vector an MPI CGS 27023A for 24 hr. with an expression cassette in the E1a region containing the trans- Substrate Zymography gene cDNA and driven by the cytomegalovirus promoter/enhancer Supernatants from human MACS-isolated CD34 (5 103 ) cells (Hattori et al., 2001b).”
- Angiogenesis in health and disease (2003, background): “, presumably because it is an EC survival factor and mobilizes EPCs and HSC”
- The biology of VEGF and its receptors (2003, background): “and increases production of B cells and generation of immature myeloid cell”
- Impaired recruitment of bone-marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth (2001, background): “VEGFR1 + cells are co-mobilized with VEGFR2 + CEPs to tumors VEGF not only induces mobilization of CEPs but also hematopoietic stem and progenitor cell”