Skip to main content

Hepatocyte Transplantation Techniques: Large Animal Models

  • Protocol
Hepatocyte Transplantation

Part of the book series: Methods in Molecular Biology ((MIMB,volume 481))

Abstract

The poor hepatocyte engraftment efficiency and the low level of their expansion in the host liver are a major limitation to cell therapy for the treatment of life-threatening liver diseases. Many rodent models have shown that liver repopulation via transplanted hepatocytes occurs only when liver growth capacity is impaired for an extended period of time. However, these models are not transposable to the clinics and to date there is no safe method to achieve this result in a clinical setting.

Therefore, it is necessary to define on large animal models strategies that provide to transplanted hepatocytes sufficient proliferation stimuli to induce their division and that could permit a direct extrapolation to humans. Such procedures should be transposable to patients. We have defined a protocol of liver partial portal branch embolisation and shown that it induces the proliferation of transplanted hepatocytes in non-human primates (Macaca mulatta). This animal model is also appropriate to evaluate the lentiviral-mediated ex vivo gene therapy approach, since simian hepatocytes are efficiently transduced by HIV-1-derived lentivirus vectors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Fisher, R. A., Strom, S. C. (2006) Human hepatocyte transplantation: worldwide results. Transplantation 82, 441–449.

    Article  PubMed  Google Scholar 

  2. Weber, A., Mahieu-Caputo, D., Hadchouel, M., et al. (2006) Hepatocyte transplantation: studies in preclinical models. J Inherit Metab Dis 29,436–441.

    Article  PubMed  Google Scholar 

  3. Allen, K., Soriano, E. (2001) Liver cell transplantation: the road to clinical application. J Lab Clin Med 138, 298–311.

    Article  PubMed  CAS  Google Scholar 

  4. Grompe, M. (2006) Principles of therapeutic liver repopulation. J Inherit Metab Dis 29, 421–425.

    Article  PubMed  Google Scholar 

  5. Azuma, H., Paulk, N., Ranade, A., et al. (2007) Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/Il2rg-/mice. Nat Biotechnol 25,903–910.

    Article  PubMed  CAS  Google Scholar 

  6. Makuuchi, M., Thai, B. L., Takayasu, K., etal. (1990) Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery 107, 521–527.

    PubMed  CAS  Google Scholar 

  7. Ilan, Y., Roy-Chowdhury, N., Prakash, R., et al. (1997) Massive repopulation of rat liver by transplantation of hepatocytes into specific lobes of the liver and ligation of portal vein branches to other lobes. Transplantation 64, 8–13.

    Article  PubMed  CAS  Google Scholar 

  8. Eguchi, S., Rozga, J., Lebow, L. T., et al. (1996) Treatment of hypercholesterolemia in the Watanabe rabbit using allogeneic hepatocellular transplantation under a regeneration stimulus. Transplantation 62, 588–593.

    Article  PubMed  CAS  Google Scholar 

  9. Dagher, I., Boudechiche, L., Branger, J., et al. (2006) Efficient hepatocyte engraftment in a nonhuman primate model after partial portal vein embolization. Transplantation 82, 1067–1073.

    Article  PubMed  Google Scholar 

  10. Nguyen, T. H., Birraux, J., Wildhaber, B., et al. (2006) Ex vivo lentivirus transduction and immediate transplantation of uncultured hepatocytes for treating hyperbilirubinemic Gunn rat. Transplantation 82, 794–803.

    Article  PubMed  Google Scholar 

  11. Nguyen, T. H., Oberholzer, J., Birraux, J., et al. (2002) Highly efficient lentiviral vector-mediated transduction of nondividing, fully reimplantable primary hepatocytes. Mol Ther 6,199–209.

    Article  PubMed  CAS  Google Scholar 

  12. Andreoletti, M., Loux, N., Vons, C., et al. (2001) Engraftment of autologous retrovirally transduced hepatocytes after intraportal transplantation into nonhuman primates: implication for ex vivo gene therapy. Hum Gene Ther 12, 169–179.

    Article  PubMed  CAS  Google Scholar 

  13. Parouchev, A., Nguyen, T. H., Dagher, I., et al. (2006) Efficient ex vivo gene transfer into non- human primate hepatocytes using HIV-1 derived lentiviral vectors. J Hepatol 45,99–107.

    Article  PubMed  CAS  Google Scholar 

  14. Vons, C., Loux, N., Simon, L., et al. (2001) Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases. Transplantation 72, 811.

    Article  PubMed  CAS  Google Scholar 

  15. Cosset, F. L., Takeuchi, Y., Weiss, R., et al. (1995) High-titer packaging cells producing recombinant retrovirus resistant to human serum. J Virol 69, 7430–7436.

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Weber, A., Groyer-Picard, MT., Dagher, I. (2009). Hepatocyte Transplantation Techniques: Large Animal Models. In: Dhawan, A., Hughes, R. (eds) Hepatocyte Transplantation. Methods in Molecular Biology, vol 481. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59745-201-4_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-201-4_8

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-172-1

  • Online ISBN: 978-1-59745-201-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics