title: Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages.
abstract: Stem/progenitors have been identified intrahepatically in the canals of Hering and extrahepatically in glands of the biliary tree. Glands of the biliary tree (peribiliary glands) are tubulo-alveolar glands with mucinous and serous acini, located deep within intrahepatic and extrahepatic bile ducts. We have shown that biliary tree stem/progenitors (BTSCs) are multipotent, giving rise in vitro and in vivo to hepatocytes, cholangiocytes or pancreatic islets. Cells with the phenotype of BTSCs are located at the bottom of the peribiliary glands near the fibromuscular layer. They are phenotypically heterogeneous, expressing transcription factors as well as surface and cytoplasmic markers for stem/progenitors of liver (e.g. SOX9/17), pancreas (e.g. PDX1) and endoderm (e.g. SOX17, EpCAM, NCAM, CXCR4, Lgr5, OCT4) but not for mature markers (e.g. albumin, secretin receptor or insulin). Subpopulations co-expressing liver and pancreatic markers (e.g. PDX1(+)/SOX17(+)) are EpCAM(+/-), and are assumed to be the most primitive of the BTSC subpopulations. Their descendants undergo a maturational lineage process from the interior to the surface of ducts and vary in the mature cells generated: pancreatic cells in hepatopancreatic ducts, liver cells in large intrahepatic bile ducts, and bile duct cells along most of the biliary tree. We hypothesize that there is ongoing organogenesis throughout life, with BTSCs giving rise to hepatic stem cells in the canals of Hering and to committed progenitors within the pancreas. The BTSCs are likely to be central to normal tissue turnover and injury repair and to be key elements in the pathophysiology of liver, pancreas and biliary tree diseases, including oncogenesis.
authors.affiliation: Department of Health Sciences, University of Rome Foro Italico, Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Carpino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cardinale
authors.forename: Paolo
authors.initials: P
authors.lastname: Onori
authors.forename: Antonio
authors.initials: A
authors.lastname: Franchitto
authors.forename: Pasquale Bartolomeo
authors.initials: PB
authors.lastname: Berloco
authors.forename: Massimo
authors.initials: M
authors.lastname: Rossi
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Wang
authors.forename: Rossella
authors.initials: R
authors.lastname: Semeraro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Anceschi
authors.forename: Roberto
authors.initials: R
authors.lastname: Brunelli
authors.forename: Domenico
authors.initials: D
authors.lastname: Alvaro
authors.forename: Lola M
authors.initials: LM
authors.lastname: Reid
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology; D017734:Bile Ducts, Extrahepatic / Q000166:cytology*; D001653:Bile Ducts, Intrahepatic / Q000166:cytology*; D001659:Biliary Tract / Q000166:cytology* / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D005704:Gallbladder / Q000166:cytology / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000502:physiology; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000502:physiology; D010641:Phenotype; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014157:Transcription Factors