title: Hepatocyte-conditioned medium sustains endothelial differentiation of human hematopoietic-endothelial progenitors.
abstract: Liver neo-angiogenesis plays a fundamental role in physiological and pathological processes such as regeneration, cirrhosis, autoimmune hepatitis, and alcoholic liver disease. How liver parenchymal cells influence angiogenesis is largely unknown. We studied the influence of soluble factors released by hepatocytes on hematopoietic and endothelial cell differentiation. Human CD34+ cells cultured for several weeks in a hepatocyte-conditioned medium gradually decrease the expression of CD34 and CD133 markers (i.e. after 4 weeks from 85% and 69%, respectively, to 6% and 3%, respectively), whereas expression of CD144 and CD14 cell markers increased (from 2% and 8%, respectively, to 54% and 55%, respectively). The cells' capacity to form hematopoietic colonies in methylcellulose declined with time, whereas they acquired endothelial morphology, expressed endothelial markers, and incorporated into newly forming vascular structures both in vitro and in vivo. Cultured single CD34+ cells formed colonies expressing both hematopoietic (CD45+) and endothelial (CD144+) markers, suggesting they constitute a bona fide hemangioblast population.
  
  
  CONCLUSIONS
  This system allowed subsequent stages of differentiation of hematopoietic cells to endothelial cells to be defined, underlining the strict interrelationship between endothelial and hematopoietic cells in a hepatocyte environment.
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Bordoni
authors.forename: Tonino
authors.initials: T
authors.lastname: Alonzi
authors.forename: Lucia
authors.initials: L
authors.lastname: Zanetta
authors.forename: Daniele
authors.initials: D
authors.lastname: Khouri
authors.forename: Annarita
authors.initials: A
authors.lastname: Conti
authors.forename: Marco
authors.initials: M
authors.lastname: Corazzari
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Antoniotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pisani
authors.forename: Francesca
authors.initials: F
authors.lastname: Tognoli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dejana
authors.forename: Marco
authors.initials: M
authors.lastname: Tripodi
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015820:Cadherins; D017077:Culture Media, Conditioned; D017493:Leukocyte Common Antigens; D000099152:Cadherin 5; C516769:PTPRC protein, human