Human cord blood-derived cells can differentiate into hepatocytes in the mouse liver with no evidence of cellular fusion.
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.
Newsome
Philip N
PN
Department of Hepatology, Chancellor's Building, University of Edinburgh, Edinburgh EH16 4SB, Scotland, UK. P.Newsome@ed.ac.uk
Johannessen
Ingolfur
I
Boyle
Shelagh
S
Dalakas
Evangelos
E
McAulay
Karen A
KA
Samuel
Kay
K
Rae
Frances
F
Forrester
Lesley
L
Turner
Marc L
ML
Hayes
Peter C
PC
Harrison
David J
DJ
Bickmore
Wendy A
WA
Plevris
John N
JN
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