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. 2007 May 1;6(1):59–73. doi: 10.1111/j.1582-4934.2002.tb00311.x

Neoductular progenitor cells regenerate hepatocytes in severely damaged liver: a comparative ultrastructural study

E Mandache 1,✉, Cristina Vidulescu 1,2, Mihaela Gherghiceanu 1, P Dragomir 1, L M Popescu 1,2
PMCID: PMC6740071  PMID: 12003669

Abstract

In severely injured liver, stem cells give rise to progeny that tend to replace lost hepatocytes. Neoductular reaction appears as an inherent stage of liver reconstruction following severe damage caused by different pathological mechanisms. Few ultrastructural types of progenitor cells have been described, and some molecular phenotypes of progenitor stages have been characterized, but the details of the differentiation process are largely unknown. We prepared for light and electron microscopy examination human liver from biopsies of patients with chronic active hepatitis, and rat liver with allyl alcohol‐induced periportal necrosis. We found that progenitor neoductular cells acquire the hepatocytic polarity pattern during a multi‐step process apparently involving cell migration and dissolution of neoductular basement membrane. An intermediate stage with “mixed” ductular and hepatocytic polarity was described.

Keywords: liver regeneration, neoductular cells, intermediate progenitor stages, hepatocyte polarity, basement membrane, chronic active hepatitis, periportal necrosis

References

  • 1. Sigal S.H., Brill S., Fiorino A.S., Reid L.M., The liver as a stem cell and lineage system, Am J. Physiol., 263 ( Gastrointest. Liver Physiol 26): G139–G148, 1992. [DOI] [PubMed] [Google Scholar]
  • 2. Brill S., Holst P., Sigal S., Zvibel I., Fiorino A., Ochs A., Somasundaran U., Reid L.M., Hepatic progenitor populations in embryonic, neonatal and adult liver, P.S.E.M.B., 204: 261–269, 1993. [DOI] [PubMed] [Google Scholar]
  • 3. Golding M., Sarraf C., Lalani N., Alison M., Reactive biliary epithelium: the product of a pluripotential stem cell compartment Hum. Pathol., 27: 872–884, 1996. [DOI] [PubMed] [Google Scholar]
  • 4. Alison M., Liver stem cells: a two compartment system, Curr. Op. Cell Biol., 10: 710–715, 1998. [DOI] [PubMed] [Google Scholar]
  • 5. Strain A.J., Crosby H.A., Hepatic stem cells, Gut, 46: 743–745, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Petersen B.E., Bowen W.C., Patrene, K.D. , Mars W.M., Sullivan A.K., Murase N., Boggs S.S., Greenberger J.S., Goff J.P., Bone marrow as a potential source of hepatic oval cells, Science, 284: 1168–1170, 1999. [DOI] [PubMed] [Google Scholar]
  • 7. Theise N.D., Badve S., Sakena R., Henegariu O., Sell S., Crawford J.M. Krause D.S., Derivation of hepatocytes from bone marrow cells in mice after radiation ‐ induced myeloablation, Hepatology, 31: 235–240, 2000. [DOI] [PubMed] [Google Scholar]
  • 8. Theise N.D., Nimmakayalu M., Gardner R, Illei P.B., Morgan G., Teperman L., Henegariu O., Krause D.S., Liver from bone marrow in humans, Hepatology 32: 11–16, 2000. [DOI] [PubMed] [Google Scholar]
  • 9. Constantinescu S.N., Stem cell generation and choice of fate: role of cytokines and cellular microenvironment, J. Cell. Mol. Med., 4: 233–248, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Sell S., Heterogeneity and plasticity of hepatocyte lineage cells, Hepatology, 33: 738–750, 2001. [DOI] [PubMed] [Google Scholar]
  • 11. Roskams T., de Vos R., Desmet V., “Undifferentiated progenitor cells” in focal nodular hyperplasia of the liver, Histopathology, 28: 291–299, 1996. [DOI] [PubMed] [Google Scholar]
  • 12. Sell S., Electron microscopic identification of putative liver stem cells and intermediate hepatocytes following periportal necrosis induced in rats by allyl alcohol, Stem Cells, 15: 378–385, 1997. [DOI] [PubMed] [Google Scholar]
  • 13. Hsia C.C., Evarts R.P., Nakatsuhasa H., Marsden E.R., Thorgeirsson S.S., Occurrence of oval‐type cells in hepatitis B virus associated human hepatocarcinogenesis, Hepatology, 16: 1327–1333, 1992. [DOI] [PubMed] [Google Scholar]
  • 14. Liang Y.R., Cheng R.X., Shen M., Guo Y.X., Su X.S., A further study on capillary‐like bile ductules proliferation in chronic active hepatitis, Chin. Med. J., 103: 623–628, 1990. [PubMed] [Google Scholar]
  • 15. Sasaki M., Nakanuma Y., Ho S.B., Kim Y.S., Increased MUC6 apomucin expression is a characteristic of reactive biliary epithelium in chronic viral hepatitis, J. Pathol., 185: 191–198, 1998. [DOI] [PubMed] [Google Scholar]
  • 16. Roskams T., Desmet V., Ductular reaction and its diagnostic significance, Seminars in Diagnostic Pathology, 15: 259–269, 1998. [PubMed] [Google Scholar]
  • 17. Lazaro C.A., Rhim J.A., Yamada Y., Fausto N., Generation of hepatocytes from oval cell precursors in culture, Cancer Res., 58: 5514–22, 1998. [PubMed] [Google Scholar]
  • 18. Arterburn L.M., Zurlo J., Yager J.D., Overton R.M., Heifetz A.H., A morphological study of differentiated hepatocytes in vitro , Hepatology, 21: 175–187, 1995. [PubMed] [Google Scholar]
  • 19. Blaheta R.A., Kronenberger B., Woitasek D., Auth M.K.H., Scholtz M., Weber S., Schuldes H., Encke A., Markus B.H., Dedifferentiation of human hepatocytes by extracellular matrix proteins in vitro: quantitative and qualitative investigation of cytokeratin 7,8,18,19 and vimentin filaments, J. Hepatol., 28: 677–690, 1998. [DOI] [PubMed] [Google Scholar]
  • 20. Yavorkovsky L., Lai E., Ilic Z., Sell S., Participation of small intraportal stem cells in the restitutive response of the liver to periportal necrosis induced by allyl alcohol, Hepatology, 21: 1702–1712, 1995. [PubMed] [Google Scholar]
  • 21. Golding M., Sarraf C.E., Lalani N., Anilkumar T.V., Edwards R.J., Nagy P., Thorgeirsson S.S., Alison M.R., Oval cell differentiation into hepatocytes in the acetylaminofluorene‐treated regenerating rat liver, Hepatol., 22: 1243–1253, 1995. [DOI] [PubMed] [Google Scholar]
  • 22. Alison, M. , Golding M., Lalani N., Nagy P., Thorgeirsson S., Sarraf C., Wholesale hepatocytic differentiation in the rat from ductular oval cells, the progeny of biliary stem cells, J. Hepatol., 26: 343–352, 1997. [DOI] [PubMed] [Google Scholar]
  • 23. Lee J.‐H., Rim H.‐J., Sell S., Heterogeneity of the “oval‐cell” response in the hamster liver during cholangiocarcinogenesis following Clonorchis sinensis infection and dimethylnitrosamine treatment, J. Hepatol., 26: 1313–1323, 1997. [DOI] [PubMed] [Google Scholar]
  • 24. Roskams T., de Vos R., van Eyken P., Myazaki H., van Damme B., Desmet V., Hepatic OV‐6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man, J. Hepatol., 29: 455–463, 1998. [DOI] [PubMed] [Google Scholar]
  • 25. Ray M.B., Mendenhall C.L., French S.W., Gartside P.S., Veterans Administration Cooperative Study Group, Bile duct changes in alcoholic liver disease, Liver 13: 36–45, 1993. [DOI] [PubMed] [Google Scholar]
  • 26. Theise N.D., Saxena R., Portmann B.C., Thung S.N., Yee H., Chiriboga L., Kumar A., Crawford J.M., The canals of Hering and hepatic stem cells, Hepatology, 30: 1425–1433, 1999. [DOI] [PubMed] [Google Scholar]
  • 27. Libbrecht L., Desmet V., van Damme B., Roskams T., Deep intralobular extension of human hepatic ‘progenitor cells’ correlates with parenchymal inflammation in chronic viral hepatitis: can ‘progenitor cells’ migrate?, J. Pathol. 192: 373–378, 2000. [DOI] [PubMed] [Google Scholar]

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