TY - JOUR
T1 - Differentiation of liver epithelial (stem-like) cells into hepatocytes induced by coculture with hepatic stellate cells
AU - Nagai, Hirokazu
AU - Terada, Kunihiko
AU - Watanabe, Go
AU - Ueno, Yasuharu
AU - Aiba, Namiko
AU - Shibuya, Tomomi
AU - Kawagoe, Masami
AU - Kameda, Takashi
AU - Sato, Mitsuru
AU - Senoo, Haruki
AU - Sugiyama, Toshihiro
N1 - Funding Information:
This work was supported in part by a grant for the Research for the Future Program from the Japan Society for the Promotion of Science (JSPS-RFTF 98I00201), by Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (11794032, 11558101), by Foundation of Promotion of Cancer Research in Japan, by the Naito Foundation, and by Intelligent Cosmos Academic Foundation.
PY - 2002
Y1 - 2002
N2 - The liver is believed to contain stem cells that can differentiate into either hepatocytes or biliary epithelial cells. In the present study, we established a nonhepatocytic epithelial cell line from the normal livers of adult rats. The established cells, designated HSL cells, were immunoreactive against α-fetoprotein, but neither albumin nor cytokeratin 19. To demonstrate the differentiation potential of HSL cells in vitro, the cells were cocultured with hepatic stellate cells as a mixture or separately using insert wells. Consequently, although coculture with hepatic stellate cells rendered HSL cells able to produce albumin, the mixed coculture system mimicking the hepatic environment elicited this phenomenon more effectively than the separated coculture system. In conclusion, HSL cells have immature properties and the potential to differentiate into mature cells. Not only the extracellular matrices but also soluble factors, which are produced by hepatic stellate cells, induce this maturation, demonstrating the importance of the hepatic environment for hepatocyte differentiation.
AB - The liver is believed to contain stem cells that can differentiate into either hepatocytes or biliary epithelial cells. In the present study, we established a nonhepatocytic epithelial cell line from the normal livers of adult rats. The established cells, designated HSL cells, were immunoreactive against α-fetoprotein, but neither albumin nor cytokeratin 19. To demonstrate the differentiation potential of HSL cells in vitro, the cells were cocultured with hepatic stellate cells as a mixture or separately using insert wells. Consequently, although coculture with hepatic stellate cells rendered HSL cells able to produce albumin, the mixed coculture system mimicking the hepatic environment elicited this phenomenon more effectively than the separated coculture system. In conclusion, HSL cells have immature properties and the potential to differentiate into mature cells. Not only the extracellular matrices but also soluble factors, which are produced by hepatic stellate cells, induce this maturation, demonstrating the importance of the hepatic environment for hepatocyte differentiation.
KW - Albumin
KW - Coculture
KW - Cytokeratin 19
KW - Hepatic stellate cell
KW - Hepatic stem cell
KW - Liver epithelial cell
KW - Transferrin
KW - α-Fetoprotein
KW - α1-Antitrypsin
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U2 - 10.1016/S0006-291X(02)00406-0
DO - 10.1016/S0006-291X(02)00406-0
M3 - Article
C2 - 12054673
AN - SCOPUS:18444419136
VL - 293
SP - 1420
EP - 1425
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 5
ER -