Transplantation of conditionally immortalized hepatocytes to treat hepatic encephalopathy

Ingo K. Schumacher, Tomoyoshi Okamoto, Byung Ho Kim, Namita Roy Chowdhury, Jayanta Roy-Chowdhury, Ira J. Fox

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Transplantation of hepatocytes has been shown to provide metabolic support during liver failure in experimental models. The potential clinical application of hepatocyte transplantation, however, is limited by the need for readily available, well-characterized cells, and a worldwide shortage of donor organs. A clonal hepatocyte cell line that could be grown economically in vitro and would exhibit a differentiated, nontransformed pheriotype following transplantation would be an attractive solution to this problem. To test this alternative, primary Lewis rat hepatocytes were conditionally immortalized by retroviral transduction with a thermolabile mutant Simian virus 40 (SV40) large T antigen. The cloned immortalized cells proliferate in culture at 33°C and stop growing at 37°C to 39°C. Transplanted into normal livers, these hepatocytes integrate normally into liver cords. When transplanted into the spleens of portacaval-shunted rats, they protect recipients from hyperammonemia-induced hepatic encephalopathy. The cells engrafted in the spleen exhibit normal morphology, secrete bile, and express albumin messenger RNA. The protection from hyperammonemia is reversed by splenectomy. These studies show that hepatocytes can be conditionally immortalized, expanded in culture, and are capable of providing metabolic support in chronic liver insufficiency. Safeguards that could make these cells clinically useful can be accomplished using currently available technology.

Original languageEnglish (US)
Pages (from-to)337-343
Number of pages7
JournalHepatology
Volume24
Issue number2
DOIs
StatePublished - Aug 1996

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Hepatic Encephalopathy
Hepatocytes
Transplantation
Hyperammonemia
Spleen
Hepatic Insufficiency
Simian virus 40
Liver
Viral Tumor Antigens
Liver Failure
Splenectomy
Bile
Albumins
Theoretical Models
Tissue Donors
Technology
Cell Line
Messenger RNA

ASJC Scopus subject areas

  • Hepatology

Cite this

Transplantation of conditionally immortalized hepatocytes to treat hepatic encephalopathy. / Schumacher, Ingo K.; Okamoto, Tomoyoshi; Kim, Byung Ho; Chowdhury, Namita Roy; Roy-Chowdhury, Jayanta; Fox, Ira J.

In: Hepatology, Vol. 24, No. 2, 08.1996, p. 337-343.

Research output: Contribution to journalArticle

Schumacher, Ingo K. ; Okamoto, Tomoyoshi ; Kim, Byung Ho ; Chowdhury, Namita Roy ; Roy-Chowdhury, Jayanta ; Fox, Ira J. / Transplantation of conditionally immortalized hepatocytes to treat hepatic encephalopathy. In: Hepatology. 1996 ; Vol. 24, No. 2. pp. 337-343.
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