Prolonged survival of mice with acute liver failure with transplantation of monkey hepatocytes cultured with an antiapoptotic pentapeptide V5

Kimiaki Tanaka, Naoya Kobayashi, Alejandro Soto Gutierrez, Jorge David Rivas-Carrillo, Nalu Navarro-Alvarez, Yong Chen, Michiki Narushima, Atsushi Miki, Teru Okitsu, Hirofumi Noguchi, Noriaki Tanaka

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Background. Because hepatocyte transplantation has been considered to be an attractive method to treat acute liver failure (ALF), efficient recovery of hepatocytes and maintenance of differentiated hepatocyte functions is of extreme importance. We here report the usefulness of an antiapoptotic pentapeptide V5, composed of Val-Pro-Met-Leu-Lys, in the monkey hepatocyte cultures. Methods. We evaluated albumin production, metabolizing abilities of ammonia, lidocaine, and diazepam of monkey hepatocytes cultured with V5. The protein expression of apoptosis-associated molecules was analyzed using power blot analysis. An unwoven cloth inoculated with V5-treated monkey hepatocytes was transplanted on the surface of the spleen of both SCID mice and Balb/c mice suffering from ALF induced by 90% hepatectomy. Results. When 100 μM V5 was utilized, ammonia-, lidocaine- and diazepam- metabolizing capacities and albumin production ability were significantly increased in V5-treated monkey hepatocytes. Such hepatocytes showed decreased Annexin V binding and increased the expression of anti-apoptotic and/or cytoprotective molecules, including Ku70, NF-κB, IKAP, hILP/XIAP, IκB, and CAS. Transplantation of the cloth containing the monkey hepatocytes significantly improved blood levels of glucose and ammonia and encephalopathy score and prolonged the survival of the mice with ALF. Conclusions. The present work clearly demonstrates the usefulness of V5 for maintaining the functions of monkey hepatocytes in tissue culture.

Original languageEnglish (US)
Pages (from-to)427-437
Number of pages11
JournalTransplantation
Volume81
Issue number3
DOIs
StatePublished - Feb 2006

Keywords

  • Acute liver failure
  • Apoptosis
  • Hepatocyte transplantation
  • Hepatocytes
  • Ku70
  • V5

ASJC Scopus subject areas

  • Transplantation

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    Tanaka, K., Kobayashi, N., Gutierrez, A. S., Rivas-Carrillo, J. D., Navarro-Alvarez, N., Chen, Y., Narushima, M., Miki, A., Okitsu, T., Noguchi, H., & Tanaka, N. (2006). Prolonged survival of mice with acute liver failure with transplantation of monkey hepatocytes cultured with an antiapoptotic pentapeptide V5. Transplantation, 81(3), 427-437. https://doi.org/10.1097/01.tp.0000188693.48882.18