- 作者：Rossella Semeraro ; Guido Carpino ; Vincenzo Cardinale ; Paolo Onori ; Raffaele Gentile ; Alfredo Cantafora ; Antonio Franchitto ; Cristina Napoli ; Maurizio Anceschi ; Roberto Brunelli ; Daniela Bosco ; Alessia Torrice ; Lola Reid ; Eugenio Gaudio ; Domenico Alvaro
- 关键词：PDX-1 ; Pancreatic and duodenal homeobox 1 ; SOX17 ; SRY (sex determining region Y)-box 17 ; hHpSCs ; human hepatic stem/progenitor cells ; PBGs ; peribiliary glands ; hBTSCs ; human biliary tree stem/progenitor cells ; FBS ; foetal bovine serum ; KM ; Kubota medium
- 刊名：Journal of Hepatology
- 出版年：2012
- 出版时间：November, 2012
- 年：2012
- 卷：57
- 期：5
- 页码：987-994
- 全文大小：2310 K
Background & Aims
Biliary tree, liver, and pancreas share a common embryological origin. We previously demonstrated the presence of stem/progenitor cells of endodermal origin in the adult human extrahepatic biliary tree. This study evaluated the human foetal biliary trees as sources of stem/progenitor cells of multiple endodermal-derived mature fates.Methods
Human foetal intrahepatic and extrahepatic biliary tree tissues and isolated cells were tested for cytoplasmic and surface markers of stem cells and committed progenitors, as well as endodermal transcription factors requisite for a liver versus pancreatic fate. In vitro and in vivo experiments were conducted to evaluate the potential mature fates of differentiation.
Results
Foetal biliary tree cells proliferated clonogenically for more than 1 month on plastic in a serum-free Kubota medium. After culture expansion, cells exhibited multipotency and could be restricted to certain lineages under defined microenvironments, including hepatocytes, cholangiocytes, and pancreatic islet cells. Transplantation of foetal biliary tree cells into the livers of immunodeficient mice resulted in effective engraftment and differentiation into mature hepatocytes and cholangiocytes.
Conclusions
Foetal biliary trees contain multipotent stem/progenitor cells comparable with those in adults. These cells can be easily expanded and induced in vitro to differentiate into liver and pancreatic mature fates, and engrafted and differentiated into mature cells when transplanted in vivo. These findings further characterise the development of these stem/progenitor cell populations from foetuses to adults, which are thought to contribute to liver and pancreas organogenesis throughout life.