Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1

M. A S Moore, K. Hattori, B. Heissig, J. H. Shieh, S. Dias, Ronald Crystal, S. Rafii

Research output: Contribution to journalArticle

241 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)36-47
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume938
Publication statusPublished - 18 Jul 2001
Externally publishedYes

Fingerprint

Angiopoietin-1
Hematopoietic Stem Cells
Vascular Endothelial Growth Factor A
Angiopoietins
Platelets
Stem cells
Serum
Granulocyte-Macrophage Progenitor Cells
Bone Marrow
Bone
Genes
CXCR4 Receptors
Monocytes
Blood Platelets
T-cells
Macrophages
Endothelial cells
Chemokines
Megakaryocytes
SCID Mice

Keywords

  • Angioblast
  • Chemokine
  • Endothelium
  • Hematopoiesis
  • Stem cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1. / Moore, M. A S; Hattori, K.; Heissig, B.; Shieh, J. H.; Dias, S.; Crystal, Ronald; Rafii, S.

In: Annals of the New York Academy of Sciences, Vol. 938, 18.07.2001, p. 36-47.

Research output: Contribution to journalArticle

@article{a1bef614ca5349c6a7773a9f29c5fd8f,
title = "Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1",
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 = "Angioblast, Chemokine, Endothelium, Hematopoiesis, Stem cell",
author = "Moore, {M. A S} and K. Hattori and B. Heissig and Shieh, {J. H.} and S. Dias and Ronald Crystal and S. Rafii",
year = "2001",
month = "7",
day = "18",
language = "English",
volume = "938",
pages = "36--47",
journal = "Annals of The Lyceum of Natural History of New York",
issn = "0890-6564",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1

AU - Moore, M. A S

AU - Hattori, K.

AU - Heissig, B.

AU - Shieh, J. H.

AU - Dias, S.

AU - Crystal, Ronald

AU - Rafii, S.

PY - 2001/7/18

Y1 - 2001/7/18

N2 - 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.

AB - 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.

KW - Angioblast

KW - Chemokine

KW - Endothelium

KW - Hematopoiesis

KW - Stem cell

UR - http://www.scopus.com/inward/record.url?scp=20244375370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20244375370&partnerID=8YFLogxK

M3 - Article

VL - 938

SP - 36

EP - 47

JO - Annals of The Lyceum of Natural History of New York

JF - Annals of The Lyceum of Natural History of New York

SN - 0890-6564

ER -