Effective hepatocyte transplantation using rat hepatocytes with low asialoglycoprotein receptor expression

Hirohiko Ise, Toshio Nikaido, Naoki Negishi, Nobuhiro Sugihara, Fumitaka Suzuki, Toshihiro Akaike, Uichi Ikeda

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Abstract

Development of a reliable method of isolating highly proliferative potential hepatocytes provides information crucial to progress in the field of hepatocyte transplantation. The aim of this study was to develop reliable hepatocyte transplantation using highly proliferative, eg, progenitor-like hepatocytes, based on asialoglycoprotein receptor (ASGPR) expression levels for hepatocyte transplantation. We have previously reported that mouse hepatocytes with low ASGPR expression levels have highly proliferative potential and can be used as progenitor-like hepatocytes. We therefore fractionated F344 male rat hepatocytes expressing low and high levels of ASGPR and determined the liver repopulation capacity of hepatocytes according to low and high ASGPR expression in the liver. Next, 2 × 105 cells of each type were transplanted into female liver regenerative model dipeptidyl peptidase-deficient rats, and we estimated the rate of liver repopulation by the transplanted hepatocytes in the host liver, as determined by recognition of the Sry gene on the Y-chromosome. At 60 days after hepatocyte transplantation, the transplanted hepatocytes occupied ∼76% of the total hepatocyte mass in the case of the transplantation of hepatocytes with low ASGPR expression, but accounted for ∼12% and 17% of the mass in the case of the transplantation of hepatocytes with high ASGPR expression and unfractionated hepatocytes, respectively. In conclusion, these findings suggest that hepatocytes with low ASGPR expression can result in normal liver function and a high repopulation capacity in vivo. These results provide insight into development of a strategy for effective liver repopulation using transplanted hepatocytes.

Original languageEnglish
Pages (from-to)501-510
Number of pages10
JournalAmerican Journal of Pathology
Volume165
Issue number2
DOIs
Publication statusPublished - Aug 2004

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Asialoglycoprotein Receptor
Hepatocytes
Transplantation
Liver
sry Genes
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Effective hepatocyte transplantation using rat hepatocytes with low asialoglycoprotein receptor expression. / Ise, Hirohiko; Nikaido, Toshio; Negishi, Naoki; Sugihara, Nobuhiro; Suzuki, Fumitaka; Akaike, Toshihiro; Ikeda, Uichi.

In: American Journal of Pathology, Vol. 165, No. 2, 08.2004, p. 501-510.

Research output: Contribution to journalArticle

Ise, Hirohiko ; Nikaido, Toshio ; Negishi, Naoki ; Sugihara, Nobuhiro ; Suzuki, Fumitaka ; Akaike, Toshihiro ; Ikeda, Uichi. / Effective hepatocyte transplantation using rat hepatocytes with low asialoglycoprotein receptor expression. In: American Journal of Pathology. 2004 ; Vol. 165, No. 2. pp. 501-510.
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