In Vitro expanded human fetal pancreatic cells differentiate into hepatocytes and cholangiocytes upon treatment with dexamethasone and functionally engraft the liver in a model of toxin-induced liver damage

C Jorns, G Nowak, S Thowfeequ, S Begum, B G Ericzon, D Tosh, S Sumitran-Holgersson

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: The appearance of hepatic foci in the pancreas has beendescribed in animal experiments as well as in human pathology. Plasticityamong endoderm-deriv ed organs also exists during fetal development inrodents. Evidence for conversion of human pancreatic cells to liver cells islacking. We investigated the developmental plasticity between the pancreasand the liver in human fetal tissues.

Materials and Methods: Cell culture and molecular techniques were used toisolate, characterize and expand cells from 7–8 week old human fetalpancreata (HFP). These cells at various passages were transpla nted intonude mice with liver injury and tested for functional capacity in vivo.

Results: We present evidence that amylase or EPCAM-expressing cellsisolated from HFP cultured with fibroblast growth factor 2 (FGF2) anddexamethasone (DX) lose expression of pancreatic markers and differentiatetowards hepatocytes or cholangiocyte-like cells. Liver cell differentiation isbased on the expression of liver markers albumin and cytokeratin 19. Whentransplanted in vivo into nude mice treated with retrorsine, the amylase+cells successfully engrafted and functionally differentiated into hepatic cellsexpressing human albumin, dipeptidyl peptidase, gammaglutamyltranspep-tidase and were functional (e.g. synthesized glycogen), while EPCAM+ cellsformed bile ducts.

Conclusions: These data indicate that fetal pancreatic cells have a uniquecapacity to alter their gene expression profile in response to FGF2 anddexamethasone. It may be possible to generate an unlimited supply ofhepatocytes in vitro from an additional tissue source that can be stimulatedto differentiate into hepatocytes when required.
Original languageEnglish
Article number408.3
Pages (from-to)437
Number of pages1
JournalXenotransplantation
Volume14
Issue number5
DOIs
Publication statusPublished - 2007
EventJoint Meeting of the International Xenotransplantation Association (IXA), the International Pancreas and Islet Transplant Association (IPITA), and the Cell Transplant Society (CTS) - Minneapolis, USA United States
Duration: 15 Sep 200720 Sep 2007

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