Treatment of acute liver failure in mice by hepatocyte xenotransplantation

Tsuyoshi Yamamoto, Nalú Navarro-Alvarez, Alejandro Soto-Gutierrez, Takeshi Yuasa, Masaya Iwamuro, Yasuhiro Kubota, Masayuki Seita, Hironobu Kawamoto, Shahid M. Javed, Eisaku Kondo, Hirofumi Noguchi, Satoru Kobayashi, Shuhei Nakaji, Naoya Kobayashi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Liver diseases still have a high mortality even though liver transplantation has become a standard treatment. Currently, hepatocyte transplantation has been proposed as another promising strategy. One limitation is the availability of human livers as a source of hepatocytes. Because of an unlimited supply, the use of porcine hepatocytes might address this problem. Regardless of the source, once isolated hepatocytes lose specific functionality due to the loss of the natural microenvironment. For this reason, we tested the ability of a self-assembling peptide nanofiber (SAPNF) to provide a provisional three-dimensional (3D) support to interact with cells to control their function in vivo. Isolated porcine hepatocytes were embedded in SAPNF, or collagen type I and transplanted by direct injection into the splenic pulp of SCID mice suffering from acute liver failure (ALF) by 90% hepatectomy. SAPNF porcine hepatocyte transplantation produced engraftment that was far superior to that obtained using collagen and prolonged the survival of mice with ALF, in contrast with controls. An ultrastructural evaluation using transmission electron microscopy indicated extensive cell-cell communication and preservation of hepatocyte architecture. The transplanted SAPNF hepatocytes showed higher expression of albumin and PAS and lower apoptotic events assessed by TUNEL staining. Hepatocytes culture in a truly 3D network allows in vivo maintaining of differentiated functions, and once transplanted between widely divergent species can function to correct acute liver failure in mice and prolong their survival.

Original languageEnglish
Pages (from-to)799-806
Number of pages8
JournalCell Transplantation
Volume19
Issue number6-7
DOIs
Publication statusPublished - 2010

Keywords

  • Acute liver failure
  • Hepatocyte transplantation
  • Hepatocytes
  • Self-assembling peptide nanofiber
  • Xenotransplantation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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  • Cite this

    Yamamoto, T., Navarro-Alvarez, N., Soto-Gutierrez, A., Yuasa, T., Iwamuro, M., Kubota, Y., Seita, M., Kawamoto, H., Javed, S. M., Kondo, E., Noguchi, H., Kobayashi, S., Nakaji, S., & Kobayashi, N. (2010). Treatment of acute liver failure in mice by hepatocyte xenotransplantation. Cell Transplantation, 19(6-7), 799-806. https://doi.org/10.3727/096368910X508915