Human haemato-endothelial precursors: cord blood CD34+ cells produce haemogenic endothelium

PLoS One. 2012;7(12):e51109. doi: 10.1371/journal.pone.0051109. Epub 2012 Dec 4.

Abstract

Embryologic and genetic evidence suggest a common origin of haematopoietic and endothelial lineages. In the murine embryo, recent studies indicate the presence of haemogenic endothelium and of a common haemato-endothelial precursor, the haemangioblast. Conversely, so far, little evidence supports the presence of haemogenic endothelium and haemangioblasts in later stages of development. Our studies indicate that human cord blood haematopoietic progenitors (CD34+45+144-), triggered by murine hepatocyte conditioned medium, differentiate into adherent proliferating endothelial precursors (CD144+CD105+CD146+CD31+CD45-) capable of functioning as haemogenic endothelium. These cells, proven to give rise to functional vasculature in vivo, if further instructed by haematopoietic growth factors, first switch to transitional CD144+45+ cells and then to haematopoietic cells. These results highlight the plasticity of haemato-endhothelial precursors in human post-natal life. Furthermore, these studies may provide highly enriched populations of human post-fetal haemogenic endothelium, paving the way for innovative projects at a basic and possibly clinical level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, CD34 / metabolism*
  • Cadherins / metabolism
  • Cell Adhesion / drug effects
  • Cell Differentiation / drug effects
  • Cell Shape / drug effects
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Fetal Blood / cytology*
  • Hemangioblasts / cytology*
  • Hemangioblasts / drug effects
  • Hemangioblasts / metabolism
  • Hematopoiesis / drug effects
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Humans
  • Immunophenotyping
  • Infant, Newborn
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Phenotype

Substances

  • Antigens, CD
  • Antigens, CD34
  • Cadherins
  • Culture Media, Conditioned
  • cadherin 5
  • Leukocyte Common Antigens

Grants and funding

Ministero della Salute (The Italian Ministry of Health), Rome, Italy (RF2006-411189); Associazione Italiana per la Ricerca sul Cancro (AIRC) (The Italian Association for Cancer Research), Milan, Italy; MIUR, Ministero Università e Ricerca Scientifica (The Ministry of Education, University and Research), Tavola Valdese OPM., Regione Lazio Italy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.