Human liver-specific nanocarrier in a novel mouse xenograft model bearing noncancerous human liver tissue

Yoshifumi Matsuura, Hiroshi Yagi, Sachiko Matsuda, Osamu Itano, Koichi Aiura, Shun'Ichi Kuroda, Masakazu Ueda, Yuukou Kitagawa

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

For the targeted delivery of genes and drugs to the human liver, hepatitis B virus (HBV) envelope L particles, which form hollow nanoparticles and display a peptide that is indispensable for liver-specific infection by HBV in humans, should be a useful tool. To test the efficacy of these particles in vivo, in the present study we generated a small animal model harboring a functional human liver tissue xenograft. An anti-asialo GM1 antibody was administered to SCID mice to induce the depletion of natural-killer-cell-dependent immune responsibility and then the mice underwent transplantation of a noncancerous liver tissue originating in humans into the kidney capsule. Interestingly, human liver tissues were engrafted in 58% of the animals at least for 14 days shown by a human hepatocyte-specific antibody. The engineered HBV nanoparticles which contained fluorescent chemicals could selectively bind to the xenograft in these immune-deficient mice when they were administered systemically. These results suggested that the model animal was usable to demonstrate the efficacy of the nanoparticles that could deliver chemicals specific to the normal human liver tissue by systemic administration, which will facilitate the study of human liver cell biology, drug metabolism and infections with hepatotropic viruses.

Original languageEnglish
Pages (from-to)65-72
Number of pages8
JournalEuropean Surgical Research
Volume46
Issue number2
DOIs
Publication statusPublished - 2011 Feb

Fingerprint

Heterografts
Liver
Hepatitis B virus
Nanoparticles
Animal Models
SCID Mice
Antibodies
Infection
Natural Killer Cells
Pharmaceutical Preparations
Capsules
Cell Biology
Hepatocytes
Transplantation
Viruses
Kidney
Peptides
Genes

Keywords

  • Liver
  • Mouse xenograft model
  • Nanocarrier

ASJC Scopus subject areas

  • Surgery

Cite this

Human liver-specific nanocarrier in a novel mouse xenograft model bearing noncancerous human liver tissue. / Matsuura, Yoshifumi; Yagi, Hiroshi; Matsuda, Sachiko; Itano, Osamu; Aiura, Koichi; Kuroda, Shun'Ichi; Ueda, Masakazu; Kitagawa, Yuukou.

In: European Surgical Research, Vol. 46, No. 2, 02.2011, p. 65-72.

Research output: Contribution to journalArticle

Matsuura, Yoshifumi ; Yagi, Hiroshi ; Matsuda, Sachiko ; Itano, Osamu ; Aiura, Koichi ; Kuroda, Shun'Ichi ; Ueda, Masakazu ; Kitagawa, Yuukou. / Human liver-specific nanocarrier in a novel mouse xenograft model bearing noncancerous human liver tissue. In: European Surgical Research. 2011 ; Vol. 46, No. 2. pp. 65-72.
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