Human vasculogenesis ex vivo: Embryonal aorta as a tool for isolation of endothelial cell progenitors

Giulio Alessandri, Marina Girelli, Gianluca Taccagni, Augusto Colombo, Roberto Nicosia, Arnaldo Caruso, Manuela Baronio, Stefano Pagano, Lidia Cova, Eugenio Parati

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Vasculogenesis, the de novo formation of new blood vessels from undifferentiated precursor cells or angiobiasts, has been studied with experimental in vivo and ex vivo animal models, but its mechanism is poorly understood, particularly in humans. We used the aortic ring assay to investigate the angioforming capacity of aortic explants from 11 - to 12-week-old human embryos. After being embedded in collagen gels, the aorta rings produced branching capillary-like structures formed by mesenchymal spindle cells that lined a capillary-like lumen and expressed markers of endothelial differentiation (CD31, CD34, von Willebrand factor [vWF], and fms-like tyrosine kinase-1 [FIk-1]/vascular endothelial growth factor receptor 2 [VEGFR2]), The cell linings of these structures showed ultrastructural evidence of endothelial differentiation, The neovascular proliferation occurred primarily in the outer aspects of aortic rings, thus suggesting that the new vessels mainly arose from immature endothelial precursor cells localized in the outer layer of the aortic stroma, ie, a process of vasculogenesis rather than angiogenesis. The undifferentiated mesenchymal cells (CD34+/CD31-), isolated and cultured on collagen-fibronectin, differentiated into endothelial cells expressing CD31 and vWF. Furthermore, the CD34+/CD31 + cells were capable of forming a network of capillary-like structures when cultured on Matrigel. This is the first reported study showing the ex vivo formation of human microvessels by vasculogenesis. Our findings indicate that the human embryonic aorta is a rich source of CD34+/CD31 - endothelial progenitor cells (angioblasts), and this information may prove valuable in studies of vascular regeneration and tissue bioengineering.

Original languageEnglish
Pages (from-to)875-885
Number of pages11
JournalLaboratory Investigation
Volume81
Issue number6
Publication statusPublished - 2001

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Aorta
von Willebrand Factor
Blood Vessels
Collagen
Endothelial Cells
Vascular Endothelial Growth Factor Receptor-1
Bioengineering
Vascular Endothelial Growth Factor Receptor-2
Differentiation Antigens
Microvessels
Fibronectins
Regeneration
Embryonic Structures
Animal Models
Gels
Endothelial Progenitor Cells

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Alessandri, G., Girelli, M., Taccagni, G., Colombo, A., Nicosia, R., Caruso, A., ... Parati, E. (2001). Human vasculogenesis ex vivo: Embryonal aorta as a tool for isolation of endothelial cell progenitors. Laboratory Investigation, 81(6), 875-885.

Human vasculogenesis ex vivo : Embryonal aorta as a tool for isolation of endothelial cell progenitors. / Alessandri, Giulio; Girelli, Marina; Taccagni, Gianluca; Colombo, Augusto; Nicosia, Roberto; Caruso, Arnaldo; Baronio, Manuela; Pagano, Stefano; Cova, Lidia; Parati, Eugenio.

In: Laboratory Investigation, Vol. 81, No. 6, 2001, p. 875-885.

Research output: Contribution to journalArticle

Alessandri, G, Girelli, M, Taccagni, G, Colombo, A, Nicosia, R, Caruso, A, Baronio, M, Pagano, S, Cova, L & Parati, E 2001, 'Human vasculogenesis ex vivo: Embryonal aorta as a tool for isolation of endothelial cell progenitors', Laboratory Investigation, vol. 81, no. 6, pp. 875-885.
Alessandri G, Girelli M, Taccagni G, Colombo A, Nicosia R, Caruso A et al. Human vasculogenesis ex vivo: Embryonal aorta as a tool for isolation of endothelial cell progenitors. Laboratory Investigation. 2001;81(6):875-885.
Alessandri, Giulio ; Girelli, Marina ; Taccagni, Gianluca ; Colombo, Augusto ; Nicosia, Roberto ; Caruso, Arnaldo ; Baronio, Manuela ; Pagano, Stefano ; Cova, Lidia ; Parati, Eugenio. / Human vasculogenesis ex vivo : Embryonal aorta as a tool for isolation of endothelial cell progenitors. In: Laboratory Investigation. 2001 ; Vol. 81, No. 6. pp. 875-885.
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AU - Taccagni, Gianluca

AU - Colombo, Augusto

AU - Nicosia, Roberto

AU - Caruso, Arnaldo

AU - Baronio, Manuela

AU - Pagano, Stefano

AU - Cova, Lidia

AU - Parati, Eugenio

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