Peribiliary glands of biliary tree as a niche of multipotent stem cells

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Peribiliary glands are located along the large bile ducts. They are found in human and majority of the animals. Other than mucous production, their function had not been defined until recently. But nowadays the question of their multiple functions is actively studied. Due to the last years reports peribiliary glands contain multipotent stem cells, which can differentiate into hepatocytes, cholangiocytes or pancreatic islets cells. The structure and function of peribiliary glands, known experimental models and perspectives of peribiliary glands use in regenerative medicine are discussed in the review.

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About the authors

E. I Sharipova

Kazan (Volga region) Federal University; Kazan State Medical University

I. M Gazizov

Kazan (Volga region) Federal University; Kazan State Medical University

AA. A Gumerova

Kazan (Volga region) Federal University

A. P Kiassov

Kazan (Volga region) Federal University


  1. Carpino G., Cardinale V., Onori P. et al. Biliary tree stem/ progenitor cells in glands of extrahepatic andintraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages. J. Anat. 2012; 220(2): 186-99.
  2. Nakanuma Y., Hoso M., Sanzen T. et al. Microstructure and development of the normal and pathologic biliary tract in humans,including blood supply. A review. Microsc. Res. Tech. 1997; 15: 552-70.
  3. Cardinale V., Wang Y., Carpino G. et al. The biliary tree - are reservoir of multipotent stem cells. Gastroenterology & Hepatology 2012; 9: 231-40.
  4. Spitz L. Choledochal cyst. Surg. Gynecol. Obstet. 1978; 147: 444-52.
  5. Terada T., Nakanuma Y. Development of human intrahepatic peribiliary glands. Histological, keratin immunohistochemical, and mucus histochemical analyses. Lab. Invest. 1993; 68: 261-9.
  6. Terada T., Kida T., Nakanuma Y. Extrahepatic peribiliary glands express a-amylase isozymes, trypsin and pancreatic lipase: an immunohistochemical analysis. Hepatology 1993; 18: 803-8.
  7. Terada T., Nakanuma Y. Pancreatic lipase is a useful phenotypicmarker of intrahepatic large and septal bile ducts, peribiliary glands, and their malignant counterparts. Mod. Pathol. 1993; 6: 419-26.
  8. Royce S.G., Hughes N.R., Binos S. et al. Vertebrate phylogeny of antigen D10: identification of a conserved foregut cell lineage. Histochem. Cell Biol. 2000; 114(2): 125-35.
  9. Katayanagi K., Kono N., Nakanuma Y. Isloation, culture and characterization of biliary epithelial cells from different anatomical levels of the intrahepatic and extrahepatic biliary tree from a mouse. Liver 1998; 18: 90-8.
  10. Cardinale V., Wang Y., Carpino G. Multipotent stem cells in the biliary tree. Ital. J. Anat. Embryol. 2010; 115(1-2): 85-90.
  11. Cardinale V. et al. Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes and pancreatic islets. Hepatology 2011; 54: 2159-72.
  12. Saito K., Nakanuma Y. Lactoferrin and lysozyme in the intrahepatic bile duct of normal livers and hepatolithiasis. An. immunohistochemical study. J. Hepatol. 1992; 15(1-2): 147-53.
  13. Nakanuma Y., Katayanagi K., Terada T., Saito K. Intrahepatic peribiliary glands of humans. I. Anatomy, developvent and presumed functions. J. Gastroenterol. Gepatol. 1994; 9(1): 75-9.
  14. Song S.Y., Gannon M., Washington M.K. et al. Expansion of Pdx1-expressing pancreatic epithelium and islet neogenesis in transgenic mice overexpressing transforming growth factor a. Gastroenterology. 1999; 117: 1416-26.
  15. Lanzoni G., Oikawa T., Wang Y. et al. Concise Review: Clinical Programs of stem cell therapies for liver and pancreas. Stem Cells 2013: 31: 2047-60.
  16. Oikawa T., Kamiya A., Zeniya M. et al. SALL4, a stem cell biomarker for liver cancers. Hepatology 2013; 57: 1469-83.
  17. Yoon S.M., Gerasimidou D., Kuwahara R. et al. Epithelial cell adhesion molecule (EpCAM] marks hepatocytes newly derived from stem/progenitor cells in humans. Hepatology 2011; 53: 964-73.
  18. Sutton M.E., op den Dries S., Koster M.H. et al. Regeneration of human extrahepatic biliary epithelium: the peribiliary glands as progenitor cell compartment. Liver Int. 2012: 32(4):554-9.
  19. Kuver R., Savard, C.E., Lee et al. Murine gallbladder epithelial cells can differentiate into hepatocyte-like cells in vitro. Am. J. Physiol. Gastrointest. Liver Physiol. 2007; 293: G944-G955.
  20. Wang Y., Lanzoni G., Carpino G. et al. Biliary tree stem cells, precursorsto pancreatic committed progenitors: Evidence for life-long pancreaticorganogenesis. Stem Cells 2013; 31: 1966-79.
  21. Schmelzer E., Zhang L., Bruce A. et al. Human hepatic stem cellsfrom fetal and postnatal donors. J. Exp. Med. 2007; 204: 1973-87.
  22. Wang Y., Yao H-l, Barbier C. et al. Lineage-dependent epithelial mesenchymal paracrine signals dictate growth versus differentiation of human hepatic stem cells to adult fates. Hepatology 2010; 52: 1443-54.
  23. Андреева Д.И., Газизов И.М., Йылмаз Т.С. и др. Возможные направления дифференцировки мононуклеаров пуповинной крови человека в регенерирующей печени крыс. Клеточная трансплантология и тканевая инженерия 2013; VIII (3): 95-100.
  24. Шафигуллина А.К., Трондин А.А., Бурганова Г.Р. и др. Сравнение различных методов выделения, мечения и трансплантации звездчатых клеток печени крысы. Клеточная трансплантология и тканевая инженерия 2013; VIII (3): 147-51.
  25. Zhang L., Theise N., Chua M., et al. Human hepatic stem cells and hepatoblasts: Symmetry between Liver Development and Liver Regeneration. Hepatology 2008; 48: 1598-1607.
  26. Kubota H., Reid L.M. Clonogenic hepatoblasts, common precursors for hepatocytic and biliary lineages, are lacking classical major histocompatibility complex class I antigens. PNAS USA 2000; 97: 12132-7.
  27. Schmelzer E., Zhang L., Bruce A., et al. Human hepatic stem cells from fetal and postnatal donors. Journal of Experimental Medicine. 2007; 204: 1973-87.
  28. Schmelzer E., Wauthier E., Reid L.M. Phenotypes of pluripotent human hepatic progenitors. Stem Cell 2006; 24: 1852-8.
  29. Schmelzer E., Reid LM. Telomerase activity in human hepatic stem cells, hepatoblasts and hepatocytes from neonatal, pediatric, adult and geriatric donors. Eur. J. Hepatology and Gastroenterol. 2009; 21: 1191-8.
  30. Semeraro R., Carpino G., Cardinale V. et al. Multipotent Stem/ Progenitor Cells in the Human Foetal Biliary Tree. J. Hepatology 2012; 220: 186-99.
  31. Furth M.E., Wang Y., Cardinale V. et al. Stem Cell Populations Giving Rise to Liver, Biliary Tree and Pancreas. In: Sell S, ed. The Stem Cells Handbook, 2nd Edition. New York City, New York: Springer Science Publishers, NY; 2013.
  32. Koblas T., Zacharovova K., Berkova Z. et al. Isolation and characterization of human CXCR4-positive pancreatic cells. Folia Biol. (Praha). 2007; 53: 13-22.
  33. Lardon J., Rooman I., Bouwens L. Nestin expression in pancreatic stellate cells and angiogenic endothelial cells. Histochem. Cell Biol. 2002; 117: 535-40.
  34. Lardon J., Corbeil D., Huttner W.B. et al. Stem cell marker prominin-1/AC133 is expressed in duct cells of the adult human pancreas. Pancreas. 2008; 36: e1-6.
  35. Seaberg R.M., Smukler S.R., Kieffer T.J. et al. Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat. Biotechnol. 2004; 22: 1115-24.
  36. Hori Y., Fukumoto M., Kuroda Y. Enrichment of putative pancreatic progenitor cells from mice by sorting for prominin1 (CD133) and platelet-derived growth factor receptor beta. Stem Cells 2008; 26: 2912-20.
  37. Huch M., Dorrell C., Boj S.F. et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 2013; 494: 247-50.
  38. Jiang W., Sui X., Zhang D. et al. CD24: a novel surface marker for PDX1-positive pancreatic progenitors derived from human embryonic stem cells. Stem Cells 2011; 29: 609-17.
  39. Schaffer A.E., Freude K.K., Nelson S.B. et al. Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitors. Dev. Dyn. 2010; 18: 1022-9.
  40. Zaret K. Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation. Nature Reviews 2008; 9: 329-4.

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