Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1 Conference Paper
| Authors: | Moore, M. A. S.; Hattori, K.; Heissig, B.; Shieh, J.H.; Dias, S.; Crystal, R. G.; Rafii, S. |
| Title: | Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1 |
| Conference Title: | 3rd International Conference and Workshop on Hematopoietic Stem Cells |
| Abstract: | The chemokine stroma-derived factor-1 (SDF-1) is produced within the bone marrow and mediates chemokinesis and chemotaxis on a variety of cell types that express the CXCR4 receptor. SDF-1-responsive cell types include monocytes and macrophages, B and T lymphocytes, platelets and megakaryocytes, and CD34+ cells, including both hematopoietic progenitors and stem cells. We have used intravenous injection of a replication-incompetent adenovector expressing the SDF-1 gene to elevate serum levels of SDF-1 in Balb/c and SCID mice. Within 3 to 5 days there was a marked leukocytosis, predominantly involving monocytes, and a three-fold increase in platelets. In addition, AdSDF-1 mobilized CFU-GM, CFU-s, and cells with long-term repopulating potential. We have identified a bone marrow-derived, circulating endothelial stem cell characterized by expression of the VEGFR2 (Flk-1/KDR). This cell exhibits a chemotactic and chemokinetic response to SDF-1 and VEGF. We have elevated serum levels of VEGF165 using intravenous adenovector gene delivery and compared this to an adenovector expressing angiopoietin-1 alone or in combination with VEGF. VEGF elevation was associated with rapid mobilization of hematopoietic stem and progenitor cells and a population of Flk-1-positive endothelial progenitors. In contrast angiopoietin induced a delayed mobilization of endothelial and hematopoietic progenitors. The combination of VEGF and angiopoietin produced a more prolonged elevation of these progenitors in the circulation with increased proliferation of capillaries and expansion of sinusoidal spaces in the marrow. |
| Keywords: | vasculotropin; controlled study; vascular endothelial growth factor a; nonhuman; receptors, vascular endothelial growth factor; conference paper; t lymphocyte; animal cell; mouse; animals; mice; cd34 antigen; vasculotropin receptor; thrombocyte; bone marrow; spleen; granulocyte macrophage colony stimulating factor; animal experiment; mice, scid; neovascularization, pathologic; mice, inbred balb c; b lymphocyte; genetic vectors; stem cell; endothelium cell; chemokine; chemotaxis; endothelium, vascular; membrane glycoproteins; splenomegaly; hematopoietic stem cells; stem cells; cell count; hematopoiesis; hematopoietic stem cell; receptor protein-tyrosine kinases; monocyte; macrophage; cytokine release; endothelium; colony-forming units assay; leukocytosis; megakaryocyte; cell motility; hematopoietic stem cell mobilization; adenoviridae; virus vector; receptors, growth factor; stromal cell derived factor 1; adenovirus; chemokine receptor cxcr4; angiopoietin 1; angiopoietin-1; vascular endothelial growth factors; endothelial growth factors; chemokines, cxc; lymphokines; colony forming unit s; angioblast; chemokinesis |
| Journal Title | Annals of the New York Academy of Sciences |
| Volume: | 938 |
| Conference Dates: | 2000 Sept 14-16 |
| Conference Location: | Tübingen, Germany |
| ISBN: | 0077-8923 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2001-06-01 |
| Start Page: | 36 |
| End Page: | 47 |
| Language: | English |
| PUBMED: | 11458524 |
| PROVIDER: | scopus |
| DOI: | 10.1111/j.1749-6632.2001.tb03572.x |
| DOI/URL: | |
| Notes: | Presented at the 3rd International Conference and Workshop on Hematopoietic Stem Cells: Basic and Clinical Sciences; 2000 Sep 14-16; Tubingen, Germany -- Export Date: 21 May 2015 -- Source: Scopus |
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