[Abstract] [Full Text PDF] (in Japanese / 3768KB) [Members Only And Two Factor Auth.]

J.Jpn. Surg. Soc.. 102(3): 277-281, 2001


Feature topic

CHARACTERIZATION OF A HIGHLY PROLIFERATIVE POPULATION OF ADULT HEPATOCYTES AND ITS USE FOR TISSUE ENGINEERING

1) Tissue Regeneration Project, Hiroshima Prefecture Collaboration of Regional Entities for the Advancement of Technological Excellence, Japan Science and Technology Corporation
2) Department of Second Surgery, Hiroshima University School of Medicine, Hiroshima, Japan
3) Developmental Biology Laboratory Department of Biological Science, Graduate School of Science, Hiroshima University, Hiroshima, Japan

Chise Tateno1), Shigeru Katayama1)2), Katsutoshi Yoshizato1)3)

It is well known among cell biologists that normal hepatocytes of adult mammals are difficult to replicate repeatedly in vitro, irrespective of the fact that these cells can grow well clonally in vivo. We developed a culture medium (HCGM) wherein the normal hapatocytes of adult Fischer rats replicate repeatedly and form clonal colonies. This growth requires the presence of hepatic stellate cells (HSCs). Fractionation and separation of hepatocytes by a combination of centrifugation and cell sorting revealed the presence of a highly proliferative population of hepatocytes in the adult liver, called small-sized hepatocytes (SHs-R3). SHs-R3 showed a 3-to 4-fold higher growth potential than large-sized hepatocytes (SHs-R2) both in vitro and in vivo. The in vivo growth potential was estimated using the retrorsine-dipeptidylpeptidase IV (DPPIV)-rat model in which DPPIV-positive SHs-R3 were transplanted into the liver of retrorsine-treated DPPIV-negative mutant rats which were then subjected to two-thirds partial hepatectomy. The results of our studies suggest a close relationship between SHs-R3 and small hepatocyte-like progenitor cells, as reported by Gordon et al. We showed that the liver of adult humans also contains a highly proliferative population of hepatocytes, which possibly corresponds to SHs-R3. Research is now being undertaken to utilize this population of human hepatocytes to develop an artificial liver.


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