The Potential of Stem Cell Transplantation to Rescue the Failing Liver

  • P. L. M. Jansen
Conference paper
Part of the Developments in Hematology and Immunology book series (DIHI, volume 38)


The growing shortage of donor organs calls for new approaches in organ transplantation. Hepatocyte transplantation in animal models has revealed the possibility to repopulate a damaged liver with normal liver cells. After injection into the portal vein, hepatocytes become correctly integrated into liver cell plates and are able to divide and perform a number of functions. Interestingly, transplanted hepatocytes become polarized and are able to secrete solutes and metabolites into bile. For instance, mdr 2 -/- knock out mice lack an essential canalicular phospholipid transporter and develop severe liver disease in particular upon feeding a bile salt supplemented diet. Under these conditions they produce a bile acid-rich phospholipid-poor bile that is toxic to hepatocytes and cholangiocytes. Syngeneic mouse hepatocytes containing either wild type mouse mdr2 or transgenic human MDR3 were transplanted into the livers of these mdr 2 -/- mice and were shown to partly repopulate the liver. After transplantation the knock-out mice produced phospholipid-containing bile and appeared protected from ongoing liver damage [1]. This experiment proves several points: healthy hepatocytes transplanted into a damaged liver divide and partly repopulate the liver, the transplanted cells do not form clumps of hepatocytes not connected to the biliary tree but they integrate into the liver cell plates with a correct anatomical orientation so that they can perform the critical function of bile secretion.


Bone Marrow Cell Glycogen Storage Disease Intrahepatic Cholestasis Severe Liver Disease Fetal Liver Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    De Vree JM, Ottenhoff R, Bosma PJ, Smith AJ, Aten J, Oude Elferink RP. Correction of liver disease by hepatocyte transplantation in a mouse model of progressive familial intrahepatic cholestasis. Gastroenterology 2000; 119: 1720–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Vroemen JP, Blanckaert N, Buurman WA, Heirwegh KP, Kootstra G. Treatment of enzyme deficiency by hepatocyte transplantation in rats. J Surg Res 1985; 39:267–75.PubMedCrossRefGoogle Scholar
  3. 3.
    Oren R, Dabeva MD, Petkov PM, Hurston E, Laconi E, Shafritz DA. Restoration of serum albumin levels in nagase analbuminemic rats by hepatocyte transplantation. Hepatology 1999;29:75–81.PubMedCrossRefGoogle Scholar
  4. 4.
    Fabrega AJ, Bommineni VR, Blanchard J, Tetali S, Rivas PA, Pollak R, et al. Amelioration of analbuminemia by transplantation of allogeneic hepato-cytes in tolerized rats. Transplantation 1995;59:1362–64.PubMedCrossRefGoogle Scholar
  5. 5.
    Grompe M, Laconi E, Shafritz DA. Principles of therapeutic liver repopulation. Semin Liver Dis 1999;19:7–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Malhi H, Irani AN, Volenberg I, Schilsky ML, Gupta S. Early cell transplantation in LEC rats modeling Wilson’s disease eliminates hepatic copper with reversal of liver disease. Gastroenterology 2002;122:438–47.PubMedCrossRefGoogle Scholar
  7. 7.
    Mitchell C, Mallet VO, Guidotti JE, Goulenok C, Kahn A, Gilgenkrantz H. Liver repopulation by Bcl-x(L) transgenic hepatocytes. Am J Pathol 2002; 160:31–35.PubMedCrossRefGoogle Scholar
  8. 8.
    Fisher RA, Bu D, Thompson M, Tisnado J, Prasad U, Sterling R, et al. Defining hepatocellular chimerism in a liver failure patient bridged with hepatocyte infusion. Transplantation 2000;69:303–07.PubMedCrossRefGoogle Scholar
  9. 9.
    Strom SC, Chowdhury JR, Fox IJ. Hepatocyte transplantation for the treatment of human disease. Semin Liver Dis 1999;19:39–48.PubMedCrossRefGoogle Scholar
  10. 10.
    Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI et al. Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med 1998;338:1422–26.PubMedCrossRefGoogle Scholar
  11. 11.
    Grossman M, Raper SE, Kozarsky K, Stein EA, Engelhardt JF, Muller D, et al. Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nat Genet 1994;6:335–41.PubMedCrossRefGoogle Scholar
  12. 12.
    Sandhu JS, Petkov PM, Dabeva MD, Shafritz DA. Stem cell properties and repopulation of the rat liver by fetal liver epithelial progenitor cells. Am J Pathol 2001;159:1323–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Malhi H, Irani AN, Gagandeep S, Gupta S. Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes. J Cell Sci 2002; 115:2679–88.PubMedGoogle Scholar
  14. 14.
    Mallet VO, Mitchell C, Mezey E, et al. Bone marrow transplantation in mice leads to a minor population of hepatocytes that can be selectively amplified in vivo. Hepatology 2002;35:799–804.PubMedCrossRefGoogle Scholar
  15. 15.
    Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, et al. Liver from bone marrow in humans. Hepatology 2000;32:11–16.PubMedCrossRefGoogle Scholar
  16. 16.
    Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, et al. Bone marrow as a potential source of hepatic oval cells. Science 1999; 284:1168–70.PubMedCrossRefGoogle Scholar
  17. 17.
    Terada N, Hamazaki T, Oka M, et al. Bone marrow cells adopt the pheno-type of other cells by spontaneous cell fusion. Nature 2002; 416:542–45.PubMedCrossRefGoogle Scholar
  18. 18.
    Jansen PL, Muller M, Sturm E. Genes and cholestasis. Hepatology 2001;34: 1067–74.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • P. L. M. Jansen
    • 1
  1. 1.Department of Gastroenterology and HepatologyUniversity Hospital GroningenThe Netherlands

Personalised recommendations