Pathology & Oncology Research

, Volume 1, Issue 1, pp 23–26 | Cite as

The facultative stem cell: A new star in Liver Pathology

  • Peter Nagy


Although the unlimited capacity of hepatocytes to divide has been recently proven, more and more evidences support the existence of a primitive stem cell compartment in the liver. These cells probably do not participate in the usual maintenance of the liver mass, but they are activated in case of extensive hepatocyte injury. In vivo the oval cells show deep similarity to the primitive cells of the embryonic liver and seem to be the amplification compartment of the hepatic stem cells. A primitive epithelial cell population can be isolated from the normal liver and maintained in vitro. Studies of these two experimental systems provide most of the data about liver stem cells, which may become important for the clinical practice if we understand how their growth is regulated.

Key words

liver stem cell oval cell carcinogenesis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Arber N, Zajieek G and Ariel I.: The streaming liver II. Hepatocyte life story. Liver 8:80–82, 1988.PubMedGoogle Scholar
  2. 2.
    Aterman K: The stem cells of the liver-a selective review. J Cancer Res Clin Oncol 118:87–115, 1992.PubMedCrossRefGoogle Scholar
  3. 3.
    Bisgaard HC, Nagy P, Ton PT, Hu Z and Thorgeirsson SS: Modulation of keratin 14 and Alfa-Fetoprotein expression during hepatic oval cell proliferation and liver regeneration. J Cell Physiology 159:475–484, 1994.CrossRefGoogle Scholar
  4. 4.
    Blouin R, Blouin M, Royal I, Grenier A, Roop DR, Loranger A and Marceau N: Cytokeratin 14 expression in rat liver cells in culture and localization in vivo. Differentiation 52:45–54, 1992.PubMedCrossRefGoogle Scholar
  5. 5.
    Braled MP, Branchereau S, Breehot Ch and Ferry N: Cell lineage study in the liver using retroviral mediated gene transfer. Evidence against the streaming of hepatocytes in normal liver. Am J Pathol 144:896–905, 1994.Google Scholar
  6. 6.
    Coleman WB, Wenncrberg AE, Smith GT and Grisham JW: Regulation of the differentiation of diploid and some aneuploid rat liver epithelial (stem like) cells by the hepatic microenvironment. Am J Pathol 142:1373–1382, 1993.PubMedGoogle Scholar
  7. 7.
    Evarts RP, Nagy P, Marsden E and Thorgeirsson SS: A precursor-product relationship exists between oval cells and hepatocytes in rat liver. Carcinogenesis 8:1737–1740, 1987.PubMedCrossRefGoogle Scholar
  8. 8.
    Evans RP, Nagy P, Marsden E and Thorgeirsson SS: In situ hybridization studies on expression of albumin and alfa-feto-protein during the early stage of neoplastic transformation in rat liver. Cancer Res 47:5469–5475, 1987.Google Scholar
  9. 9.
    Factor VM, Radaeva SA and Thorgeirsson SS:Origin and fate of oval cells in Dipin induced hepatocarcinogenesis in the mouse. Am J Pathol 145:409–422, 1994.PubMedGoogle Scholar
  10. 10.
    Farber E: Imilarities in the sequence of early histological changes induced in the liver of the rat by ethionine. 2-acetylaminofluorene. and 3'methyl-4-dimethylaminoazobenzene Cancer Res 16:142–148, 1956.Google Scholar
  11. 11.
    Fausto N, Thompson NL and Bnnin L: Purification and culture of oval cells from rat liver. Cell Separation Methods 4:45–77, 1987.Google Scholar
  12. 12.
    Gerber MA, Thung SN.Shen SS, Stromever FW and Ishak KG: Phenotypic characterization of hepatic proliferation. Antigenic expression by proliferating epithelial cells in fetal liver, massive hepatic necrosis and nodular transformation of the liver. Am J Pathol 110:70–74, 1983.PubMedGoogle Scholar
  13. 13.
    Germain L, Blouin MJ and Mareeau N: Biliary epithelial and hepatocytic cell lineage relationships in embryonic rat liver as determined by the differential expression of cytokeralins Alfa-fetoprotein. albumin and cell surface exposed components. Cancer Res 48:4909–4918, 1988.PubMedGoogle Scholar
  14. 14.
    Grishain JW: Cell types in long term propagable cultures of rat liver. Am N Y Acad Sci 349:128–134, 1980.CrossRefGoogle Scholar
  15. 15.
    Havner NT, Brann L, Yaswen P, Brooks M and Fausto N: Isozyme profiles of oval cells, parenchymal cells and biliary cells isolated by centrifugal elutriation from normal and preneoplastic livers. Cancer Res 44:332–338, 1984.Google Scholar
  16. 16.
    Hsia CC, Evarls RP, Nakatsukasa N, Marsden E and Thorgeirsson SS: Occurenceof oval-type cells in hepatitis B virus associated human hepatocarcinogenesis. Hepatology 16:1327–1333, 1992.PubMedCrossRefGoogle Scholar
  17. 17.
    Inaoka Y: Significance of the so-called oval cell proliferation during azo-dye hepatocarcinogenesis. GANN 58:355–366, 1967.PubMedGoogle Scholar
  18. 18.
    Lemire JIM, Shiojiri N and Fausto N: Oval cell proliferation and the origin of small hepatocytes in liver injury induced by d-galaetosamine. Am J Pathol 139:535–552, 1991.PubMedGoogle Scholar
  19. 19.
    Lemire JM and Fausto N: Multiple Alfa-fetopiotein RNA-s in adult rat liver. Cell type-specific expression and differential regulation. Cancer Res 51:4656–4664, 1991.PubMedGoogle Scholar
  20. 20.
    Mareeau N: Cell lineage and differentiation programs in epidermal, urothelial and hepatic tissues and their neoplasms. Lab Invest 63:4–20, 1990.Google Scholar
  21. 21.
    Mareeau N, Blouin MJ, Germain L and Noel M: Role of different epithelial cell types in liver ontogenesis, regeneration and neoplasia. In Vitro Cell Dev Biol 25:336–341, 1989.CrossRefGoogle Scholar
  22. 22.
    Matins GA, Walls SS.D'Amico P Gengo TF and Sirica AE: Enzyme profile of rat bile ductular epithelial cells in reference to the resistance phenotype in hepatocarcinogenesis. Hepatology 9:477–485, 1989.CrossRefGoogle Scholar
  23. 23.
    Nagy P, Bisgaard HC and Thorgeirsson SS: Expression of hepatic transcription factors during liver development and oval cell differenciation.J Cell Biol 126:223–233, 1994.PubMedCrossRefGoogle Scholar
  24. 24.
    Nagy P Evarls RP, McMahom JB and Thorgeirsson SS: Role of TGFβ in normal differentiation and oncogenesis in rat liver. Mol Carcinogenesis 2:345–354, 1989.CrossRefGoogle Scholar
  25. 25.
    Pollen CS and Loefiler M: Stem cells attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110:1001–1020, 1990.Google Scholar
  26. 26.
    Reddy JK, Rao MS, Qureshi SA, Reddy MK, Scarpelli OG and Ealwani ND: Induction and origin of hepatocytes in rat pancreas. J Cell Biol 98:2080–2090, 1984.CrossRefGoogle Scholar
  27. 27.
    Rhim JA, Sandgren EP Degen JL, Palmiter RD and Brinsler RL: Replacement of diseased mouse liver by hepatic cell transplantation. Science 263:1149–1152, 1994.PubMedCrossRefGoogle Scholar
  28. 28.
    Schirmacher P, Rogler CE and Dienes HP: Current pathogenetic and molecular concepts in viral liver carcinogenesis. Virchows Archiv B Cell Pathol 63:71–89, 1993.Google Scholar
  29. 29.
    Schrenk D, Eisenmann-Tappe I, Gebhardt R, Mayer D, Mouelhi ME, Röhrdam E, Münzel P and Bock KW: Drug metabolizing enzyme activities in rat liver epithelial cell lines, hepatocytes and bile duct cells. Biochemical Pharmacol 41:1751–1757, 1991.CrossRefGoogle Scholar
  30. 30.
    Sell S: Is there a liver stem cell? Cancer Res 50:3811–3815, 1990.PubMedGoogle Scholar
  31. 31.
    Shah KD and Gerber MA: Development of intrahepatic bile ducts in humans possible role of laminin. Arch Pathol Lab Med 114:597–600, 1990.PubMedGoogle Scholar
  32. 32.
    Shall KD and Gerher MA: Immunohistochemical study using monoclonal CK antibodies. Arch Pathol Lab Med 113:1135–1138, 1989.Google Scholar
  33. 33.
    Sirica AE, Mathis GA, Sano N and Elmore LW: Isolation, culture and transplantation of intrahepatic biliary epithelial cells and oval cells. Pathobiology 58:44–64, 1990.PubMedCrossRefGoogle Scholar
  34. 34.
    Tatemalsn M, Ho RH, Kaku T, Ekem JK and Farber E: Studies on the proliferation and fate of oval cells in the liver of rats treated with 2-acetylaminofluorene and partial hepatectomy. Am J Pathol 114:418–430, 1984.Google Scholar
  35. 35.
    Tatematsu M, Kaku T, Medline A and Earber E: Intestinal metaplasia as a common option of oval cells in relation to cholangiofibrosis in liver of rats exposed to 2-acetylaminofluorene. Lab Invest 52:354–362, 1985.PubMedGoogle Scholar
  36. 36.
    Thung SM:The development of proliferating ductular structures in liver disease. Arch Pathol Lab Med 114:407–411, 1990.PubMedGoogle Scholar
  37. 37.
    Tsao SM and Grisham JW: Hepatocarcinomas, cholangicarcinomas and hepatoblastomas produced by chemically transformed cultured rat liver epithelial cell. Am J Pathol 129:168–181, 1987.Google Scholar
  38. 38.
    Uchida T and Peters RL: The nature and origin of proliferating bile ductules in alcoholic liver disease. Am J Clin Pathol 79:326–333, 1983.PubMedGoogle Scholar
  39. 39.
    Van Eyken P,Sciot R and Desmet V: Intrahepatic bile duet development in the rat: a cytokeratin-immunohistochemical study. Lab Invest 59:52–59, 1988.PubMedGoogle Scholar
  40. 40.
    Williams GM, Weisburger EK and Weisburger JH: Isolation and long term culture of epithelial cells from the rat liver. Exp Cell Res 69:106–112, 1971.PubMedCrossRefGoogle Scholar
  41. 41.
    Wolf HK, Burchette IL, Garcia IA and Michalopoulos G: Exocrin pancreatic tissue in human liver: a metaplastic process? Am J Surg Pathol 14:590–595, 1990.PubMedCrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 1995

Authors and Affiliations

  • Peter Nagy
    • 1
  1. 1.1st Institute of Pathology and Experimental Cancer ResearchSemmelweis Medical UniversityBudapestHungary

Personalised recommendations