Hepatocytes pp 525-534

Part of the Methods in Molecular Biology book series (MIMB, volume 640)

Human Hepatocyte Transplantation

  • Anil Dhawan
  • Stephen C. Strom
  • Etienne Sokal
  • Ira J. Fox
Protocol

Abstract

Over the last decade the interest in hepatocyte transplantation has been growing continuously and this treatment may represent an alternative clinical approach for patients with acute liver failure and life-threatening liver-based metabolic disorders. The technology also serves as the proof of concept and reference for future development in stem cell technology. This chapter reviews the field of hepatocyte transplantation from bench to bedside.

Key words

Hepatocyte transplantation collagenase cryopreservation liver tissue source GMP laboratory metabolic liver disease acute liver failure stem cells immunosuppression 

References

  1. 1.
    Pereira, S.P., McCarthy, M., Ellis, A.J., Wendon, J., Portmann, B., Rela, M. et al. (1997) Auxiliary partial orthotopic liver transplantation for acute liver failure. J. Hepatol. 26, 1010–1017.PubMedCrossRefGoogle Scholar
  2. 2.
    Mitry, R.R., Hughes, R.D., Aw, M.M., Terry, C., Mieli-Vergani, G., Girlanda, R. et al. (2003) Human hepatocyte isolation and relationship of cell viability to early graft function. Cell Transplant. 12, 69–74.PubMedCrossRefGoogle Scholar
  3. 3.
    Mitry, R.R., Dhawan, A., Hughes, R.D., Bansal, S., Lehec, S., Terry, C. et al. (2004) One liver, three recipients: segment IV from split-liver procedures as a source of hepatocytes for cell transplantation. Transplantation 77, 1614–1616.PubMedCrossRefGoogle Scholar
  4. 4.
    Kobayashi, N., Fujiwara, T., Westerman, K.A., Inoue, Y., Sakaguchi, M., Noguchi, H. et al. (2000) Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes. Science 287, 1258–1262.PubMedCrossRefGoogle Scholar
  5. 5.
    Cai, J., Ito, M., Nagata, H., Westerman, K.A., Lafleur, D., Chowdhury, J.R. et al. (2002) Treatment of liver failure in rats with end-stage cirrhosis by transplantation of immortalized hepatocytes. Hepatology 36, 386–394.PubMedCrossRefGoogle Scholar
  6. 6.
    Dan, Y.Y., Riehle, K.J., Lazaro, C., Teoh, N., Haque, J., Campbell, J.S. et al. (2006) Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages. Proc. Natl. Acad. Sci. USA 103, 9912–9917.PubMedCrossRefGoogle Scholar
  7. 7.
    Avital, I., Feraresso, C., Aoki, T., Hui, T., Rozga, J., Demetriou, A. et al. (2002) Bone marrow-derived liver stem cell and mature hepatocyte engraftment in livers undergoing rejection. Surgery 132, 384–390.PubMedCrossRefGoogle Scholar
  8. 8.
    Miki, T., Lehmann, T., Cai, H., Stolz, D.B., and Strom, S.C. (2005) Stem cell characteristics of amniotic epithelial cells. Stem Cells 23, 1549–1559.PubMedCrossRefGoogle Scholar
  9. 9.
    Ruhnke, M., Ungefroren, H., Nussler, A., Martin, F., Brulport, M., Schormann, W. et al. (2005) Differentiation of in vitro-modified human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells. Gastroenterology 128, 1774–1786.PubMedCrossRefGoogle Scholar
  10. 10.
    Strom, S.C., Dorko, K., Thompson, M.T., Pisarov, L.A., and Nussler, A.K. (1998) Large scale isolation and culture of human hepatocytes, in (Franco, D., Boudjema, K., and Varet, B. eds.) Îlots de Langerhans et hépatocytes:vers une utilisation therapeutique: Les Editions INSERM, Paris, pp. 195–205.Google Scholar
  11. 11.
    Diener, B., Utesch, D., Beer, N., Durk, H., and Oesch, F. (1993) A method for the cryopreservation of liver parenchymal cells for studies of xenobiotics. Cryobiology 30, 116–127.PubMedCrossRefGoogle Scholar
  12. 12.
    Moscioni, A.D., Roy-Chowdhury, J., Barbour, R., Brown, L.L., Roy-Chowdhury, N., Competiello, L.S. et al. (1989) Human liver cell transplantation. Prolonged function in athymic-Gunn and athymic-analbuminemic hybrid rats. Gastroenterology 96, 1546–1551.PubMedGoogle Scholar
  13. 13.
    Gupta, S., Rajvanshi, P., and Lee, C.D. (1995) Integration of transplanted hepatocytes into host liver plates demonstrated with dipeptidyl peptidase IV-deficient rats. Proc. Natl. Acad. Sci. USA 92, 5860–5864.PubMedCrossRefGoogle Scholar
  14. 14.
    Horslen, S.P. and Fox, I.J. (2004) Hepatocyte transplantation. Transplantation 77, 1481–1486.PubMedCrossRefGoogle Scholar
  15. 15.
    Fox, I.J. and Roy-Chowdhury, J. (2004) Hepatocyte transplantation. J. Hepatol. 40, 878–886.PubMedCrossRefGoogle Scholar
  16. 16.
    Krishna Vanaja, D., Sivakumar, B., Jesudasan, R.A., Singh, L., Janardanasarma, M.K., and Habibullah, C.M. (1998) In vivo identification, survival, and functional efficacy of transplanted hepatocytes in acute liver failure mice model by FISH using Y-chromosome probe. Cell Transplant. 7, 267–273.PubMedCrossRefGoogle Scholar
  17. 17.
    Sutherland, D.E., Numata, M., Matas, A.J., Simmons, R.L., and Najarian, J.S. (1977) Hepatocellular transplantation in acute liver failure. Surgery 82, 124–132.PubMedGoogle Scholar
  18. 18.
    Baumgartner, D., LaPlante-O’Neill, P.M., Sutherland, D.E., and Najarian, J.S. (1983) Effects of intrasplenic injection of hepatocytes, hepatocyte fragments and hepatocyte culture supernatants on D-galactosamine-induced liver failure in rats. Eur. Surg. Res. 15, 129–135.PubMedCrossRefGoogle Scholar
  19. 19.
    Demetriou, A.A., Reisner, A., Sanchez, J., Levenson, S.M., Moscioni, A.D., and Chowdhury, J.R. (1988) Transplantation of microcarrier-attached hepatocytes into 90% partially hepatectomized rats. Hepatology 8, 1006–1009.PubMedCrossRefGoogle Scholar
  20. 20.
    Guha, C., Parashar, B., Deb, N.J., Garg, M., Gorla, G.R., Singh, A. et al. (2002) Normal hepatocytes correct serum bilirubin after repopulation of Gunn rat liver subjected to irradiation/partial resection. Hepatology 36, 354–362.PubMedCrossRefGoogle Scholar
  21. 21.
    Park, S.M., Vo, K., Lallier, M., Cloutier, A.S., Brochu, P., Alvarez, F. et al. (2006) Hepatocyte transplantation in the Long Evans Cinnamon rat model of Wilson’s disease. Cell Transplant. 15, 13–22.PubMedCrossRefGoogle Scholar
  22. 22.
    Kocken, J.M., Borel Rinkes, I.H., Bijma, A.M., de Roos, W.K., Bouwman, E., Terpstra, O.T. et al. (1996) Correction of an inborn error of metabolism by intraportal hepatocyte transplantation in a dog model. Transplantation 62, 358–364.PubMedCrossRefGoogle Scholar
  23. 23.
    Rozga, J., Holzman, M., Moscioni, A.D., Fujioka, H., Morsiani, E., and Demetriou, A.A. (1995) Repeated intraportal hepatocyte transplantation in analbuminemic rats. Cell Transplant. 4, 237–243.PubMedCrossRefGoogle Scholar
  24. 24.
    De Vree, J.M., Ottenhoff, R., Bosma, P.J., Smith, A.J., Aten, J., and Oude Elferink, R.P. (2000) Correction of liver disease by hepatocyte transplantation in a mouse model of progressive familial intrahepatic cholestasis. Gastroenterology 119, 1720–1730.PubMedCrossRefGoogle Scholar
  25. 25.
    Habibullah, C.M., Syed, I.H., Qamar, A., and Taher-Uz, Z. (1994) Human fetal hepatocyte transplantation in patients with fulminant hepatic failure. Transplantation 58, 951–952.PubMedCrossRefGoogle Scholar
  26. 26.
    Strom, S.C., Chowdhury, J.R., and Fox, I.J. (1999) Hepatocyte transplantation for the treatment of human disease. Semin. Liver Dis. 19, 39–48.PubMedCrossRefGoogle Scholar
  27. 27.
    Schneider, A., Attaran, M., Meier, P.N., Strassburg, C., Manns, M.P., Ott, M. et al. (2006) Hepatocyte transplantation in an acute liver failure due to mushroom poisoning. Transplantation 82, 1115–1116.PubMedCrossRefGoogle Scholar
  28. 28.
    Grossman, M., Raper, S.E., Kozarsky, K., Stein, E.A., Engelhardt, J.F., Muller, D. et al. (1994) Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nat. Genet. 6, 335–341.PubMedCrossRefGoogle Scholar
  29. 29.
    Grossman, M., Rader, D.J., Muller, D.W., Kolansky, D.M., Kozarsky, K., Clark, B.J., 3rd, et al. (1995) A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia. Nat. Med. 1, 1148–1154.PubMedCrossRefGoogle Scholar
  30. 30.
    Fox, I.J., Chowdhury, J.R., Kaufman, S.S., Goertzen, T.C., Chowdhury, N.R., Warkentin, P.I. et al. (1998) Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N. Engl. J. Med. 338, 1422–1426.PubMedCrossRefGoogle Scholar
  31. 31.
    Lysy, P.A., Najimi, M., Stephenne, X., Bourgois, A., Smets, F., and Sokal, E.M. (2008) Liver cell transplantation for Crigler-Najjar syndrome type I: update and perspectives. World J. Gastroenterol. 14, 3464–3470.PubMedCrossRefGoogle Scholar
  32. 32.
    Ambrosino, G., Varotto, S., Strom, S.C., Guariso, G., Franchin, E., Miotto, D. et al. (2005) Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1. Cell Transplant. 14, 151–157.PubMedCrossRefGoogle Scholar
  33. 33.
    Strom, S.C., Fisher, R.A., Rubinstein, W.S., Barranger, J.A., Towbin, R.B., Charron, M. et al. (1997) Transplantation of human hepatocytes. Transplant. Proc. 29, 2103–2106.PubMedCrossRefGoogle Scholar
  34. 34.
    Horslen, S.P., McCowan, T.C., Goertzen, T.C., Warkentin, P.I., Cai, H.B., Strom, S.C. et al. (2003) Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder. Pediatrics 111, 1262–1267.PubMedCrossRefGoogle Scholar
  35. 35.
    Tan, N., Puppi, J., Mitry, R., Hughes, R., Lehec, S., Mieli-Vergani, G. et al. (2009) Hepatocyte transplantation followed by auxiliary liver transplantation – a novel treatment for ornithine transcarbamylase deficiency. Am. J. Transplant. 8(2), 452–457.Google Scholar
  36. 36.
    Stephenne, X., Najimi, M., Smets, F., Reding, R., de Ville de Goyet, J., and Sokal, E.M. (2005) Cryopreserved liver cell transplantation controls ornithine transcarbamylase deficient patient while awaiting liver transplantation. Am. J. Transplant. 5, 2058–2061.PubMedCrossRefGoogle Scholar
  37. 37.
    Stephenne, X., Najimi, M., Sibille, C., Nassogne, M.C., Smets, F., and Sokal, E.M. (2006) Sustained engraftment and tissue enzyme activity after liver cell transplantation for argininosuccinate lyase deficiency. Gastroenterology 130, 1317–1323.PubMedCrossRefGoogle Scholar
  38. 38.
    Sokal, E.M., Smets, F., Bourgois, A., Van Maldergem, L., Buts, J.P., Reding, R. et al. (2003) Hepatocyte transplantation in a 4-year-old girl with peroxisomal biogenesis disease: technique, safety, and metabolic follow-up. Transplantation 76, 735–738.PubMedCrossRefGoogle Scholar
  39. 39.
    Muraca, M., Gerunda, G., Neri, D., Vilei, M.T., Granato, A., Feltracco, P. et al. (2002) Hepatocyte transplantation as a treatment for glycogen storage disease type 1a. Lancet 359, 317–318.PubMedCrossRefGoogle Scholar
  40. 40.
    Dhawan, A., Mitry, R.R., Hughes, R.D., Lehec, S., Terry, C., Bansal, S. et al. (2004) Hepatocyte transplantation for inherited factor VII deficiency. Transplantation 78, 1812–1814.PubMedCrossRefGoogle Scholar
  41. 41.
    Stéphenne, X., Najimi, M., Ngoc, D.K., Smets, F., Hue, L., Guigas, B., and Sokal, E.M. (2007) Cryopreservation of human hepatocytes alters the mitochondrial respiratory chain complex 1. Cell Transplant. 16, 409–419.PubMedGoogle Scholar
  42. 42.
    Darwish, A.A., Sokal, E., Stephenne, X., Najimi, M., de Goyet Jde, V., and Reding, R. (2004) Permanent access to the portal system for cellular transplantation using an implantable port device. Liver Transplant. 10, 1213–1215.CrossRefGoogle Scholar
  43. 43.
    Fisher, R.A., Bu, D., Thompson, M., Wolfe, L., and Ritter, J.K. (2004) Optimization of conditions for clinical human hepatocyte infusion. Cell Transplant. 13, 677–689.PubMedCrossRefGoogle Scholar
  44. 44.
    Fox, I.J. and Chowdhury, J.R. (2004) Hepatocyte transplantation. Am. J. Transplant. 4 Suppl 6, 7–13.PubMedCrossRefGoogle Scholar
  45. 45.
    Terry, C., Dhawan, A., Mitry, R.R., Lehec, S.C., and Hughes, R.D. (2005) Preincubation of rat and human hepatocytes with cytoprotectants prior to cryopreservation can improve viability and function upon thawing. Liver Transplant. 11, 1533–1540.CrossRefGoogle Scholar
  46. 46.
    Balladur, P., Crema, E., Honiger, J., Calmus, Y., Baudrimont, M., Delelo, R. et al. (1995) Transplantation of allogeneic hepatocytes without immunosuppression: long-term survival. Surgery 117, 189–194.PubMedCrossRefGoogle Scholar
  47. 47.
    Miki, T., Marongiu, F., Ellis, E.C., Dorko, K., Mitamura, K., Ranade, A., Gramignoli, R., Davila, J., and Strom, S.C. (2009) Production of hepatocyte-like cells from human amnion. Methods Mol. Biol. 481, 1–14.CrossRefGoogle Scholar
  48. 48.
    Lysy, P.A., Campard, D., Smets, F., Malaise, J., Mourad, M., Najimi, M., and Sokal, E.M. (2008) Persistence of a chimerical phenotype after hepatocyte differentiation of human bone marrow mesenchymal stem cells. Cell Prolif. 41, 36–58.PubMedCrossRefGoogle Scholar
  49. 49.
    Najimi, M., Khuu, D.N., Lysy, P.A., Jazouli, N., Abarca, J., Sempoux, C., and Sokal, E.M. (2007) Adult-derived human liver mesenchymal-like cells as a potential progenitor reservoir of hepatocytes? Cell Transplant. 16, 717–728.PubMedGoogle Scholar
  50. 50.
    Campard, D., Lysy, P.A., Najimi, M., and Sokal, E.M. (2008) Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells. Gastroenterology 134, 833–848.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Anil Dhawan
    • 1
  • Stephen C. Strom
    • 2
  • Etienne Sokal
    • 3
  • Ira J. Fox
    • 4
  1. 1.King’s Cell Isolation UnitKing’s College HospitalLondonUK
  2. 2.Department of PathologyUniversity of PittsburghPittsburghUSA
  3. 3.Pediatric DepartmentUniversité Catholique de LouvainBrusselsBelgium
  4. 4.Department of SurgeryUniversity of Nebraska Medical CenterOmahaUSA

Personalised recommendations