Influence of 4-hydroxynonenal and spleen cells on primary hepatocyte culture and a novel liver-derived cell line resembling hepatocyte stem cells.
Liver is a unique mammalian organ with a great capacity of regeneration related to its function. After surgical resection or injury, hepatic cells, especially hepatocytes, can proliferate rapidly to repair the damage and to regenerate the structure without affecting the function of the liver. Loss of catalase activity during regeneration indicates that oxidative stress is present in the liver not only in pathological conditions but also as a 'physiological' factor during regeneration. As we have shown in our previous work, liver stem cell-like cells treated with 4-hydroxynonenal (HNE), a cytotoxic and growth regulating lipid peroxidation product, recover in the presence of spleen cells. In the current study we characterized this novel cell line as liver-derived progenitor/oval-like cells, (LDP/OCs), i.e. functional liver stem-like cells. We showed that LDP/OC were OV6 positive, with abundant glycogen content in the cytoplasm and expressed alpha-fetoprotein, albumin, biliverdin reductase and gamma-glutamyl transferase. Also, we compared their growth in vitro with the growth of cultured primary hepatocytes stressed with HNE and co-cultured with autologous spleen cells. The influence of spleen cells on HNE-treated primary hepatocytes and on LDP/OCs showed that spleen cells support in a similar manner the recovery of both types of liver cells indicating their important role in regeneration. Hence, LDP/OC cells may provide a valuable tool to study cell interactions and the role on HNE in liver regeneration.
Cipak
Ana
A
Rudjer Boskovic Institute, Zagreb, Croatia.
Borovic
Suzana
S
Jaganjac
Morana
M
Bresgen
Nikolaus
N
Kirac
Iva
I
Grbesa
Ivana
I
Mrakovcic
Lidija
L
Cindric
Marina
M
Scukanec-Spoljar
Mira
M
Gall-Troselj
Koraljka
K
Coric
Marijana
M
Eckl
Peter
P
Zarkovic
Neven
N
D000447:Aldehydes / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects* / Q000648:ultrastructure; D008099:Liver / Q000737:chemistry* / Q000166:cytology* / Q000187:drug effects; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology*; D013234:Stem Cells / Q000187:drug effects*
D000447:Aldehydes; C027576:4-hydroxy-2-nonenal