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Thermoreversible gelation polymer induces the emergence of hepatic stem cells in the partially injured rat liver
Author(s) -
Nagaya Masaki,
Kubota Sunao,
Suzuki Noboru,
Akashi Katsuya,
Mitaka Toshihiro
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21153
Subject(s) - hepatocyte , albumin , transferrin , pathology , chemistry , stem cell , immunohistochemistry , hepatic stellate cell , biology , microbiology and biotechnology , in vitro , medicine , biochemistry
Focal injury of the adult liver causes formation of granulomatous tissue and fibrosis. When thermoreversible gelation polymer (TGP) was applied to such defects of the rat liver, complete recovery of hepatic tissues was observed without granulation. We analyzed the mechanism of the regeneration. TGP is a chemically synthesized biocompatible polymer material whose sol‐gel transition is reversible by changing the temperature. Cooled TGP was poured into a penetration lesion of the rat liver. Immunohistochemistry and polymerase chain reaction were carried out using tissues and cultured cells isolated from ductular structures. Immunocytochemical and ultrastructural analyses were also conducted. Seven days after TGP treatment, ductular reactions were observed around the wound and ductules elongated to the injured area. Cells in the structures were alpha‐fetoprotein (AFP) positive, albumin + , CK19 + , c‐Kit + , and Thy1 + . Hepatocyte‐like cells possessing glycogen appeared around the tips of the ductules from day 9. The defect was completely replaced with hepatocytes by day 28. Cells isolated from the ductules expressed Musashi‐1, c‐Kit, Thy1, AFP, albumin, transferrin, connexin 43, and CK19. When the cultured cells were covered by TGP, they rapidly proliferated to form colonies, whereas without TGP cells gradually died. Morphologically and ultrastructurally the cells were similar to hepatocytes. They expressed not only albumin and transferrin but TAT, CYP2E1, and CCAAT/enhancer binding protein α. Some cells formed bile canaliculus‐like structures. In conclusion , TGP may trigger the initiation of hepatic stem cells in biliary ductules, and stem cell activation may occur even in the regeneration of the normal liver. (H EPATOLOGY 2006;43:1053–1062.)