[
Abstract]
[
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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
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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