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Human Fetal Aorta Contains Vascular Progenitor Cells Capable of Inducing Vasculogenesis, Angiogenesis, and Myogenesis in Vitro and in a Murine Model of Peripheral Ischemia

Authors :
Cesare Peschle
Gloria Invernici
Tommaso Rizzuti
Giulio Alessandri
Umberto Fascio
Eugenio Parati
Mauro Siragusa
Costanza Emanueli
Silvia Cristini
Paolo Madeddu
Anna Benetti
Roberto F. Nicosia
Sergio Domenico Gadau
Emilio Ciusani
Giorgio Stassi
Augusto Colombo
INVERNICI G
EMANUELI C
MADEDDU P
CRISTINI S
GADAU S
BENETTI A
CIUSANI E
STASSI G
SIRAGUSA M
NICOSIA R
PESCHLE C
FASCIO U
COLOMBO A
RIZZUTI T
PARATI E
ALESSANDRI G
Source :
The American Journal of Pathology. 170:1879-1892
Publication Year :
2007
Publisher :
Elsevier BV, 2007.

Abstract

Vasculogenesis, the formation of blood vessels in embryonic or fetal tissue mediated by immature vascular cells (ie, angioblasts), is poorly understood. We report the identification of a population of vascular progenitor cells (hVPCs) in the human fetal aorta composed of undifferentiated mesenchymal cells that coexpress endothelial and myogenic markers. Under culture conditions that promoted cell differentiation, hVPCs gave rise to a mixed population of mature endothelial and mural cells when progenitor cells were stimulated with vascular endothelial growth factor-A or platelet-derived growth factor-betabeta. hVPCs grew as nonadherent cells and, when embedded in a three-dimensional collagen gel, reorganized into cohesive cellular cords that resembled mature vascular structures. hVPC-conditioned medium contained angiogenic substances (vascular endothelial growth factor-A and angiopoietin-2) and strongly stimulated the proliferation of endothelial cells. We also demonstrate the therapeutic efficacy of a small number of hVPCs transplanted into ischemic limb muscle of immunodeficient mice. hVPCs markedly improved neovascularization and inhibited the loss of endogenous endothelial cells and myocytes, thus ameliorating the clinical outcome from ischemia. We conclude that fetal aorta represents an important source for the investigation of the phenotypic and functional features of human vascular progenitor cells.

Details

ISSN :
00029440
Volume :
170
Database :
OpenAIRE
Journal :
The American Journal of Pathology
Accession number :
edsair.doi.dedup.....679cdec2166cb08d04571102db60a7ca
Full Text :
https://doi.org/10.2353/ajpath.2007.060646