Liver repopulation by c-Met-positive stem/progenitor cells isolated from the developing rat liver

Atsushi Suzuki, Yun Wen Zheng, Katashi Fukao, Hiromitsu Nakauchi, Hideki Taniguchi

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background/Aims: Self-renewing stem cells responsible for tissue or organ development and regeneration have been recently described. To isolate such cells using flow cytometry, it should be required to find molecules expressing on their cell surfaces. We have previously reported that, on cells fulfilling the criteria for hepatic stem cells, the hepatocyte growth factor receptor c-Met is expressed specifically in the developing mouse liver. In this study, to determine whether c-Met is an essential marker for hepatic stem cells in other animal strains, we examined the potential for in vivo liver-repopulation in sorted fetal ratderived c-Met+ cells using the retrorsine model. Methodology: Using flow cytometry and monoclonal antibodies for c-Met and leukocyte common antigen CD45, fetal rat liver cells were fractionated according to the expression of these molecules. Then, cells in each cell subpopulation were sorted and transplanted into the retrorsine-treated adult rats with two-third hepatectomy. At 9 months post transplant, frequency of liver-repopulation was examined by qualitative and quantitative analyses. Results: When we transplanted c-Met+ CD45- sorted cells, many donor-derived cells formed colonies that included mature hepatocytes expressing albumin and containing abundant glycogen in their cytoplasm. In contrast, c-Met cells and CD45+ cells could not repopulate damaged recipient livers. Conclusions: High enrichment of liver-repopulating cells was conducted by sorting of c-Met+ cells from the developing rat liver. This result suggests that c-Met/HGF interaction plays a crucial role for stem cell growth, differentiation, and self-renewal in rat liver organogenesis. Since the c-Met is also expressed in the fetal mouse-derived hepatic stem cells, this molecule could be expected to be an essential marker for such cell population in the various animal strains, including human.

Original languageEnglish
Pages (from-to)423-426
Number of pages4
JournalHepato-Gastroenterology
Volume51
Issue number56
Publication statusPublished - Mar 2004
Externally publishedYes

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Stem Cells
Liver
Hepatocytes
Flow Cytometry
Proto-Oncogene Proteins c-met
CD45 Antigens
Organogenesis
Hepatectomy
Glycogen
Regeneration
Cell Differentiation
Albumins
Cytoplasm
Monoclonal Antibodies
Transplants

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Liver repopulation by c-Met-positive stem/progenitor cells isolated from the developing rat liver. / Suzuki, Atsushi; Zheng, Yun Wen; Fukao, Katashi; Nakauchi, Hiromitsu; Taniguchi, Hideki.

In: Hepato-Gastroenterology, Vol. 51, No. 56, 03.2004, p. 423-426.

Research output: Contribution to journalArticle

Suzuki, A, Zheng, YW, Fukao, K, Nakauchi, H & Taniguchi, H 2004, 'Liver repopulation by c-Met-positive stem/progenitor cells isolated from the developing rat liver', Hepato-Gastroenterology, vol. 51, no. 56, pp. 423-426.
Suzuki, Atsushi ; Zheng, Yun Wen ; Fukao, Katashi ; Nakauchi, Hiromitsu ; Taniguchi, Hideki. / Liver repopulation by c-Met-positive stem/progenitor cells isolated from the developing rat liver. In: Hepato-Gastroenterology. 2004 ; Vol. 51, No. 56. pp. 423-426.
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