The nitric oxide pathway modulates hemangioblast activity of adult hematopoietic stem cells

Steven M. Guthrie, Lisa M. Curtis, Robert N. Marnes, Gregory G. Simon, Maria B. Grant, Edward W. Scott

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

We have previously established a model inducing hematopoietic stem cell (HSC) production of circulating endothelial progenitor cells (EPCs) to revascularize ischemic injury in adult mouse retina. The unique vascular environment of the retina results in new blood vessel formation primarily from HSC-derived EPCs. Using mice deficient (-/-) in inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), we show that vessel phenotype resulting from hemangioblast activity can be altered by modulation of the NO/NOS pathway. iNOS-/- or eNOS-/- animals were engrafted with wild-type (WT) HSCs expressing green fluorescence protein (gfp +) and subjected to our adult retinal ischemia model. WT hemangioblast activity in adult iNOS-/- recipients resulted in the formation of highly branched blood vessels of donor origin, which were readily perfused indicating functionality. In contrast, eNOS-/- recipients produced relatively unbranched blood vessels with significant donor contribution that were difficult to perfuse, indicating poor functionality. Furthermore, eNOS-/- chimeras had extensive gfp + HSC contribution through-out their vasculature without additional injury. This neovascularization, via EPCs derived from the transplanted HSCs, reveals that the NO pathway can modulate EPC activity and plays a critical role in both blood vessel formation in response to injury and normal endothelial cell maintenance.

Original languageEnglish (US)
Pages (from-to)1916-1922
Number of pages7
JournalBlood
Volume105
Issue number5
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

Fingerprint

Hemangioblasts
Adult Stem Cells
Endothelial cells
Hematopoietic Stem Cells
Stem cells
Nitric Oxide Synthase Type III
Blood Vessels
Blood vessels
Nitric Oxide
Nitric Oxide Synthase Type II
Retina
Wounds and Injuries
Blood Donors
Animals
Ischemia
Endothelial Cells
Fluorescence
Maintenance
Modulation
Tissue Donors

ASJC Scopus subject areas

  • Hematology

Cite this

Guthrie, S. M., Curtis, L. M., Marnes, R. N., Simon, G. G., Grant, M. B., & Scott, E. W. (2005). The nitric oxide pathway modulates hemangioblast activity of adult hematopoietic stem cells. Blood, 105(5), 1916-1922. https://doi.org/10.1182/blood-2004-09-3415

The nitric oxide pathway modulates hemangioblast activity of adult hematopoietic stem cells. / Guthrie, Steven M.; Curtis, Lisa M.; Marnes, Robert N.; Simon, Gregory G.; Grant, Maria B.; Scott, Edward W.

In: Blood, Vol. 105, No. 5, 01.03.2005, p. 1916-1922.

Research output: Contribution to journalArticle

Guthrie, SM, Curtis, LM, Marnes, RN, Simon, GG, Grant, MB & Scott, EW 2005, 'The nitric oxide pathway modulates hemangioblast activity of adult hematopoietic stem cells', Blood, vol. 105, no. 5, pp. 1916-1922. https://doi.org/10.1182/blood-2004-09-3415
Guthrie SM, Curtis LM, Marnes RN, Simon GG, Grant MB, Scott EW. The nitric oxide pathway modulates hemangioblast activity of adult hematopoietic stem cells. Blood. 2005 Mar 1;105(5):1916-1922. https://doi.org/10.1182/blood-2004-09-3415
Guthrie, Steven M. ; Curtis, Lisa M. ; Marnes, Robert N. ; Simon, Gregory G. ; Grant, Maria B. ; Scott, Edward W. / The nitric oxide pathway modulates hemangioblast activity of adult hematopoietic stem cells. In: Blood. 2005 ; Vol. 105, No. 5. pp. 1916-1922.
@article{56b95438bb054e34aa2aa4f465035550,
title = "The nitric oxide pathway modulates hemangioblast activity of adult hematopoietic stem cells",
abstract = "We have previously established a model inducing hematopoietic stem cell (HSC) production of circulating endothelial progenitor cells (EPCs) to revascularize ischemic injury in adult mouse retina. The unique vascular environment of the retina results in new blood vessel formation primarily from HSC-derived EPCs. Using mice deficient (-/-) in inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), we show that vessel phenotype resulting from hemangioblast activity can be altered by modulation of the NO/NOS pathway. iNOS-/- or eNOS-/- animals were engrafted with wild-type (WT) HSCs expressing green fluorescence protein (gfp +) and subjected to our adult retinal ischemia model. WT hemangioblast activity in adult iNOS-/- recipients resulted in the formation of highly branched blood vessels of donor origin, which were readily perfused indicating functionality. In contrast, eNOS-/- recipients produced relatively unbranched blood vessels with significant donor contribution that were difficult to perfuse, indicating poor functionality. Furthermore, eNOS-/- chimeras had extensive gfp + HSC contribution through-out their vasculature without additional injury. This neovascularization, via EPCs derived from the transplanted HSCs, reveals that the NO pathway can modulate EPC activity and plays a critical role in both blood vessel formation in response to injury and normal endothelial cell maintenance.",
author = "Guthrie, {Steven M.} and Curtis, {Lisa M.} and Marnes, {Robert N.} and Simon, {Gregory G.} and Grant, {Maria B.} and Scott, {Edward W.}",
year = "2005",
month = "3",
day = "1",
doi = "10.1182/blood-2004-09-3415",
language = "English (US)",
volume = "105",
pages = "1916--1922",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "5",

}

TY - JOUR

T1 - The nitric oxide pathway modulates hemangioblast activity of adult hematopoietic stem cells

AU - Guthrie, Steven M.

AU - Curtis, Lisa M.

AU - Marnes, Robert N.

AU - Simon, Gregory G.

AU - Grant, Maria B.

AU - Scott, Edward W.

PY - 2005/3/1

Y1 - 2005/3/1

N2 - We have previously established a model inducing hematopoietic stem cell (HSC) production of circulating endothelial progenitor cells (EPCs) to revascularize ischemic injury in adult mouse retina. The unique vascular environment of the retina results in new blood vessel formation primarily from HSC-derived EPCs. Using mice deficient (-/-) in inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), we show that vessel phenotype resulting from hemangioblast activity can be altered by modulation of the NO/NOS pathway. iNOS-/- or eNOS-/- animals were engrafted with wild-type (WT) HSCs expressing green fluorescence protein (gfp +) and subjected to our adult retinal ischemia model. WT hemangioblast activity in adult iNOS-/- recipients resulted in the formation of highly branched blood vessels of donor origin, which were readily perfused indicating functionality. In contrast, eNOS-/- recipients produced relatively unbranched blood vessels with significant donor contribution that were difficult to perfuse, indicating poor functionality. Furthermore, eNOS-/- chimeras had extensive gfp + HSC contribution through-out their vasculature without additional injury. This neovascularization, via EPCs derived from the transplanted HSCs, reveals that the NO pathway can modulate EPC activity and plays a critical role in both blood vessel formation in response to injury and normal endothelial cell maintenance.

AB - We have previously established a model inducing hematopoietic stem cell (HSC) production of circulating endothelial progenitor cells (EPCs) to revascularize ischemic injury in adult mouse retina. The unique vascular environment of the retina results in new blood vessel formation primarily from HSC-derived EPCs. Using mice deficient (-/-) in inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), we show that vessel phenotype resulting from hemangioblast activity can be altered by modulation of the NO/NOS pathway. iNOS-/- or eNOS-/- animals were engrafted with wild-type (WT) HSCs expressing green fluorescence protein (gfp +) and subjected to our adult retinal ischemia model. WT hemangioblast activity in adult iNOS-/- recipients resulted in the formation of highly branched blood vessels of donor origin, which were readily perfused indicating functionality. In contrast, eNOS-/- recipients produced relatively unbranched blood vessels with significant donor contribution that were difficult to perfuse, indicating poor functionality. Furthermore, eNOS-/- chimeras had extensive gfp + HSC contribution through-out their vasculature without additional injury. This neovascularization, via EPCs derived from the transplanted HSCs, reveals that the NO pathway can modulate EPC activity and plays a critical role in both blood vessel formation in response to injury and normal endothelial cell maintenance.

UR - http://www.scopus.com/inward/record.url?scp=14944357281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14944357281&partnerID=8YFLogxK

U2 - 10.1182/blood-2004-09-3415

DO - 10.1182/blood-2004-09-3415

M3 - Article

C2 - 15546953

AN - SCOPUS:14944357281

VL - 105

SP - 1916

EP - 1922

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -