EurekaMag.com logo
+ Site Statistics
References:
53,623,987
Abstracts:
29,492,080
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Treatment of acute liver failure in the pig with transplantation of reversibly immortalized human hepatocytes



Treatment of acute liver failure in the pig with transplantation of reversibly immortalized human hepatocytes



Hepatology 38(4 Suppl 1): 282A, October



Purpose: Although hepatocyte transplantation (HTX) is a promising treatment for patients with liver failure, donor liver scarcity is fundamental limitation of this form of the therapy. The availability of well-characterized human hepatocyte cell lines could facilitate cell therapies such as HTX and bioartificial livers. Toward this goal, we have developed a tightly regulated human hepatocyte line. Methods: Human hepatocytes were immortalized with a retroviral vector encoding human telomerase reverse transcriptase (hTERT) and green fluorescent protein (GFP) cDNAs flanked by a pair of LoxPs. After retroviral transduction, a single cell clone was obtained using flow cytometric cell sorting followed by limiting dilution method. The resultant GFP-positive clones were super-transduced with Tamoxifen-inducible Cre recombinase expression cassette, MerCreMer. Recovery of the reverted form of hTERT-immortalized cells was conducted by Tamoxifen treatment and subsequent GFP-negative cell sorting with MoFlo. The expression of hepatocyte markers and albumin secretion was compared before and after Tamoxifen treatment. Transplantation effect of the reverted cells (1X109) into the liver were evaluated in a pig model of liver failure induce by an intravenous administration of D-galactosamine (D-gal). Results:A non-tumorigenic human hepatocyte cell line TTNT-16-T3 was established. Albumin secretion and gene expression of liver markers were increased in the reverted TTNT-16-T3 cells. Transplantation of the reverted cells via the portal vein of pigs treated with D-gal was effective to prolong the survival by providing liver support until spontaneous hepatic regeneration occurred. Conclusion: We here demonstrate reversible immortalization of human hepatocytes using Tamoxifen-induced Cre/Lox self-excision: The resulting cell line would be highly desirable for research and therapeutic applications.

(PDF 0-2 workdays service: $29.90)

Accession: 035980782

Download citation: RISBibTeXText



Related references

Transplantation of reversibly immortalized human hepatocytes for the treatment of liver failure. Hepatology 32(4 Pt 2): 402A, October, 2000

Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes. Science 287(5456): 58-62, 2000

Survival of liver failure pigs by transplantation of reversibly immortalized human hepatocytes with Tamoxifen-mediated self-recombination. Journal of Hepatology 47(1): 74-82, 2007

Transplantation of immortalized human hepatocytes as treatment for acute liver failure. Xenotransplantation 14(5): 386, 2007

Transplantation of primary and reversibly immortalized human liver cells and other gene therapies in acute liver failure and decompensated chronic liver disease. World Journal of Gastroenterology 6(5): 636-642, 2002

Treatment of surgically induced acute liver failure with transplantation of highly differentiated immortalized human hepatocytes. Cell Transplantation 9(5): 733-735, 2001

Effect of intrasplenic transplantation of immortalized human hepatocytes in the treatment of acetaminophen-induced acute liver failure SCID mice. Transplantation Proceedings 40(2): 617-619, 2008

Treatment of surgically induced acute liver failure by transplantation of conditionally immortalized hepatocytes. Transplantation 63(11): 1541-1547, 1997

Transplantation of highly differentiated immortalized human hepatocytes to treat acute liver failure. Transplantation 69(2): 202-207, 2000

Transplantation of immortalized human fetal hepatocytes prevents acute liver failure in 90% hepatectomized mice. Transplantation Proceedings 42(5): 1907-1914, 2010

Treatment of acute liver failure induced in rats by 90 percent hepatectomy by transplantation of conditionally-immortalized hepatocytes. Journal of Investigative Medicine 43(SUPPL 2): 400A, 1995

Treatment of acetaminophen-induced acute liver failure in the mouse with conditionally immortalized human hepatocytes. Journal of Hepatology 43(6): 1031-1037, 2005

Treatment of liver failure in rats with end-stage cirrhosis by transplantation of immortalized hepatocytes. Hepatology 36(2): 386-394, 2002

Improved survival of 90% hepatectomized rats by transplantation of reversibly immortalized adult human hepatocytes. Hepatology 30(4 PART 2): 513A, 1999

Treatment of fulminant liver failure by transplantation of microencapsulated primary or immortalized xenogeneic hepatocytes. Transplantation Proceedings 37(1): 527-529, 2005