title: Human cord blood-derived cells can differentiate into hepatocytes in the mouse liver with no evidence of cellular fusion.
abstract: OBJECTIVE
  Studies have indicated that stem cells have unexpected plasticity and can differentiate down a multitude of nonhematopoietic cell lineages in rodents. Our aim was to identify whether human cord blood cells, which are a rich source of stem cells, would be able to differentiate into hepatocytes when infused into nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. We also wanted to test whether such differentiated cells were the result of cellular fusion or true stem cell transdifferentiation.
  
  
  METHODS
  Unsorted mononuclear cell preparations of human cord blood were infused into sublethally irradiated NOD-SCID mice. After death, immunohistologic analysis of murine livers was performed using human specific hepatocyte, biliary, and endothelial markers. Fluorescent in situ hybridization (FISH) for mouse and human DNA was also performed.
  
  
  RESULTS
  We show that human cord blood cells have the ability to engraft into NOD-SCID liver and become mature hepatocytes. We were unable to identify any biliary or endothelial differentiation. Furthermore, we do not detect any evidence of cell fusion in any of the human cells found in the mouse liver, suggesting that human cord blood cells are capable of true transdifferentiation into hepatocytes in vivo.
  
  
  CONCLUSIONS
  We conclude that hepatocytes can derive from human cord blood cells when infused into NOD-SCID mice in the absence of fusion. The demonstration that human stem cell differentiation can occur in this murine model permits comprehensive study of human stem cell plasticity in vivo.
authors.affiliation: Department of Hepatology, Chancellor's Building, University of Edinburgh, Edinburgh EH16 4SB, Scotland, UK. P.Newsome@ed.ac.uk
authors.forename: Philip N
authors.initials: PN
authors.lastname: Newsome
authors.forename: Ingolfur
authors.initials: I
authors.lastname: Johannessen
authors.forename: Shelagh
authors.initials: S
authors.lastname: Boyle
authors.forename: Evangelos
authors.initials: E
authors.lastname: Dalakas
authors.forename: Karen A
authors.initials: KA
authors.lastname: McAulay
authors.forename: Kay
authors.initials: K
authors.lastname: Samuel
authors.forename: Frances
authors.initials: F
authors.lastname: Rae
authors.forename: Lesley
authors.initials: L
authors.lastname: Forrester
authors.forename: Marc L
authors.initials: ML
authors.lastname: Turner
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hayes
authors.forename: David J
authors.initials: DJ
authors.lastname: Harrison
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
authors.forename: John N
authors.initials: JN
authors.lastname: Plevris
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion; D005312:Fetal Blood / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID