Three dimensional culture of HepG2 liver cells on a rat decellularized liver matrix for pharmacological studies.
Three-dimensional in vitro tumor models are needed to obtain more information about drug behavior in tumors. The aim of this study is to establish a new model for hepatocellular carcinoma (HCC) using decellularized rat livers. After generating the rat liver scaffolds, HepG2 liver cancer cells were perfused via the portal vein and placed in a bioreactor for 10 days. Histology was performed to analyze cell distribution within the scaffolds. Function and tumor-related gene expression were examined by polymerase chain reaction (PCR). We evaluated the function of HepG2 cells grown on scaffolds in the presence of a well-known anti-cancer drug to investigate the potential application of our system for drug screening. The scaffolds were devoid of cellular materials and preserved extracellular matrix components. HepG2 cells grew well on the scaffolds. The PCR results showed that the cells maintained function and invasion ability at significantly higher levels than cells grown on two-dimensional (2-D) dishes or spheroids on Matrigel. Unlike the 2-D cultures, albumin secretion and alpha-fetoprotein expression in three-dimensional cultures were less susceptible to lower concentrations of the drug. Cells grown in scaffolds seemed to respond to the drug in an analogous manner to its known activity in vivo. These findings strengthen the potential use of rat liver scaffolds for screening HCC drugs.
Stem Cell Institute, Kangwon National University, Chuncheon, Gangwon, 200-701, Korea.|Department of Veterinary Surgical Sciences, College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon, 200-701, Korea.
Kamal H
KH
Hussein
Stem Cell Institute, Kangwon National University, Chuncheon, Gangwon, 200-701, Korea.|Department of Veterinary Surgical Sciences, College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon, 200-701, Korea.
Kyung M
KM
Park
Stem Cell Institute, Kangwon National University, Chuncheon, Gangwon, 200-701, Korea.
Jinn H
JH
Ghim
Stem Cell Institute, Kangwon National University, Chuncheon, Gangwon, 200-701, Korea.|Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University, Chuncheon, Gangwon, 200-701, Korea.
Se R
SR
Yang
Stem Cell Institute, Kangwon National University, Chuncheon, Gangwon, 200-701, Korea.|Department of Veterinary Surgical Sciences, College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon, 200-701, Korea.|Harvard Stem Cell Institute, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Massachusetts, 02115.
Heung M
HM
Woo
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000737:chemistry*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054457:Tissue Scaffolds / Q000737:chemistry*
drug screening; in vitro 3-D culture; liver scaffold; tumor