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TISSUE-SPECIFIC STEM CELLS

Hemogenic Endothelial Progenitor Cells Isolated from Human Umbilical Cord Blood

^aVascular Biology Program and Department of Surgery and
^bStem Cell Program and Division of Hematology, Department of Medicine, Children's Hospital Boston, Boston, Massachusetts, USA;
Departments of ^cPediatrics and
^dSurgery, Harvard Medical School, Boston, Massachusetts, USA

Key Words. Endothelial progenitor cells • Hemogenic endothelium • Umbilical cord blood • AML-1 • CD133

Correspondence: Joyce Bischoff, Ph.D., Vascular Biology Program and Department of Surgery, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA. Telephone: 617-919-2192; Fax: 617-730-0231; e-mail: joyce.bischoff{at}childrens.harvard.edu

Received December 5, 2006; accepted for publication July 9, 2007.
First published online in STEM CELLS EXPRESS   July 19, 2007.



Hemogenic endothelium has been identified in embryonic dorsal aorta and in tissues generated from mouse embryonic stem cells, but to date there is no evidence for such bipotential cells in postnatal tissues or blood. Here we identify a cell population from human umbilical cord blood that gives rise to both endothelial cells and hematopoietic progenitors in vitro. Cord blood CD34+/CD133+ cells plated at high density in an endothelial basal medium formed an endothelial monolayer and a nonadherent cell population after 14–21 days. AML-1, a factor required for definitive hematopoiesis, was detected at low levels in adherent cells and at high levels in nonadherent cells. Nonadherent cells coexpressed the endothelial marker vascular endothelial (VE)-cadherin and the hematopoietic marker CD45, whereas adherent cells were composed primarily of VE-cadherin+/CD45– cells and a smaller fraction of VE-cadherin+/CD45+ cells. Both nonadherent and adherent cells produced hematopoietic colonies in methylcellulose, with the adherent cells yielding more colony-forming units (CFU)-GEMM compared with the nonadherent cells. To determine whether the adherent endothelial cells were producing hematopoietic progenitors, single cells from the adherent population were expanded in 96-well dishes for 14 days. The clonal populations expressed VE-cadherin, and a subset expressed AML-1, -globin, and -globin. Three of 17 clonal cell populations gave rise to early CFU-GEMM hematopoietic progenitors and burst-forming unit-erythroid progenitors. These results provide evidence for hemogenic endothelial cells in human umbilical cord blood.

Disclosure of potential conflicts of interest is found at the end of this article.