The role of angiopoietins in the development of endothelial cells from cord blood CD34+ progenitors

• Published in: Blood Vol. 104; no. 7; pp. 2010 - 2019
• Main Authors: Hildbrand, Patrick, Cirulli, Vincenzo, Prinsen, Robyn C., Smith, Kent A., Torbett, Bruce E., Salomon, Daniel R., Crisa, Laura
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.10.2004; The Americain Society of Hematology
• Subjects: Angiopoietin-1 - biosynthesis; Angiopoietin-2 - biosynthesis; Antigens, CD34 - biosynthesis; Antigens, CD34 - immunology; Antigens, CD34 - metabolism; Biological and medical sciences; Blood vessels and receptors; Blotting, Western; CD11b Antigen - biosynthesis; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell Division; Cell physiology; Cells, Cultured; Collagen - pharmacology; DNA, Complementary - metabolism; Drug Combinations; Endothelial Cells - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Fetal Blood - cytology; Fetal Blood - metabolism; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Humans; Laminin - pharmacology; Microscopy, Confocal; Molecular and cellular biology; Neovascularization, Pathologic; Proteoglycans - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells - cytology; Up-Regulation; Vertebrates: cardiovascular system; Human; Angiogenesis; Endothelial cell; Postnatal; Stem cell; Blood vessel; Umbilical cord; Carcinogenesis; Cicatrization; Blood; Progenitor cell
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-12-4219

Circulating endothelial progenitors contribute to neovascularization at sites of injury and tumorigenesis in postnatal life. Yet, the molecular mechanisms initiating the endothelial developmental program of these precursors remain elusive. Here we provide evidence that endothelial development from progenitors circulating in human cord blood requires angiopoietins, a set of growth factors also involved in vascular branching during embryogenesis. We show that cord blood cells with the potential for endothelial development reside in a CD34+CD11b+ subset capable of autonomously producing and binding angiopoietins. Functionally, endogenous angiopoietin-1 regulates initial endothelial cell commitment, whereas angiopoietin-2 enhances expansion of the endothelial cell progeny. These findings suggest a role for angiopoietins as regulators of endothelial development from circulating progenitors and imply a function of angiopoietins at distinct developmental steps in postnatal angiogenesis.