In vitro cultured islet-derived progenitor cells of human origin express human albumin in severe combined immunodeficiency mouse liver in vivo.
Studies in rodents suggest the presence of a hepatopancreatic stem cell in adult pancreas that may give rise to liver cells in vivo. The aim of the present study was to determine the ability of human islet-derived cells to adopt a hepatic phenotype in vivo. Cultured human islet-derived progenitor cells that did not express albumin in vitro were stained with the red fluorescent dye PKH26 and injected into the liver of severe combined immunodeficiency mice. After 3 or 12 weeks, red fluorescent cells were detected in 11 of 15 livers and were mostly single cells that were well integrated into the liver tissue. Human albumin was found in 8 of 11 animals by immunohistochemistry, and human albumin mRNA was detected in 4 of 10 host livers. The mechanism underlying this phenomenon seems to be transdifferentiation, because human and mouse albumin were found to be expressed in distinct cells in the host liver.
von Mach
Marc-Alexander
MA
II. Medical Department, University of Mainz, Mainz, Germany. marcm@giftinfo.uni-mainz.de
Hengstler
Jan Georg
JG
Brulport
Marc
M
Eberhardt
Michael
M
Schormann
Wiebke
W
Hermes
Matthias
M
Prawitt
Dirk
D
Zabel
Bernhard
B
Grosche
Jens
J
Reichenbach
Andreas
A
Müller
Beat
B
Weilemann
Ludwig Sacha
LS
Zulewski
Henryk
H
D000418:Albumins / Q000737:chemistry*; D000818:Animals; D002454:Cell Differentiation; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D002871:Chromosome Banding; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000166:cytology*; D007621:Karyotyping; D008099:Liver / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D009930:Organic Chemicals / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors; D014183:Transplantation, Heterologous
D000418:Albumins; D005456:Fluorescent Dyes; D009930:Organic Chemicals; C070080:PKH 26; D012333:RNA, Messenger