Three dimensional culture upregulates extracellular matrix protein expression in human liver cell lines -: a step towards mimicking the liver in vivo?

被引:40
作者
Selden, C [1 ]
Khalil, M [1 ]
Hodgson, H [1 ]
机构
[1] UCL Royal Free & Univ Coll Med Sch, Ctr Hepatol, Dept Med, London NW3 2PF, England
关键词
liver; 3-dimensional culture; extracellular matrix;
D O I
10.1177/039139880002301107
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Extracellular matrix (ECM) in the liver affects the phenotype of both hepatocytes and non-parenchymal cells. To be able to mimic in vivo liver function for extracorporeal hepatic support using human cell lines, a necessary step is to upregulate the function normally seen in monolayer culture. 3-D spheroid colonies were formed by culturing single HepG2 cells encapsulated in alginate beads. ECM expression in these cultures was compared to monolayer Hep G2 cultures. The following ECM proteins were detected immunohistochemically:- collagens I, ill, V and VI, the glycoproteins fibronectin, tenascin and vitronectin, and the basement membrane protein laminin. In 3-D cultures, all proteins except tenascin were strongly expressed, as compared with weak or undetectable expression in monolayer cultures, even with 10-fold increases in the antibody concentration used. In conclusion, we have demonstrated that the 3-D environment created by alginate encapsulation of cell lines leads to cell behaviour mimicking that in vivo.
引用
收藏
页码:774 / 781
页数:8
相关论文
共 50 条
[1]   CELL CELL AND CELL MATRIX INTERACTIONS DIFFERENTIALLY REGULATE THE EXPRESSION OF HEPATIC AND CYTOSKELETAL GENES IN PRIMARY CULTURES OF RAT HEPATOCYTES [J].
BENZEEV, A ;
ROBINSON, GS ;
BUCHER, NLR ;
FARMER, SR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (07) :2161-2165
[2]   Use and outcome of liver transplantation in acetaminophen-induced acute liver failure [J].
Bernal, W ;
Wendon, J ;
Rela, M ;
Heaton, N ;
Williams, R .
HEPATOLOGY, 1998, 27 (04) :1050-1055
[3]   Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: Hepatocytes cultured in a sandwich configuration [J].
Berthiaume, F ;
Moghe, PV ;
Toner, M ;
Yarmush, ML .
FASEB JOURNAL, 1996, 10 (13) :1471-1484
[4]  
BISMUTH H, 1987, LANCET, V2, P674
[5]   Liver transplantation in Europe for patients with acute liver failure [J].
Bismuth, H ;
Samuel, D ;
Castaing, D ;
Williams, R ;
Pereira, SP .
SEMINARS IN LIVER DISEASE, 1996, 16 (04) :415-425
[6]   SUPPORT OF CULTURED-HEPATOCYTES BY A LAMININ-RICH GEL - EVIDENCE FOR A FUNCTIONALLY SIGNIFICANT SUBENDOTHELIAL MATRIX IN NORMAL RAT-LIVER [J].
BISSELL, DM ;
ARENSON, DM ;
MAHER, JJ ;
ROLL, FJ .
JOURNAL OF CLINICAL INVESTIGATION, 1987, 79 (03) :801-812
[7]  
BUCKE C, 1987, METHOD ENZYMOL, V135, P175
[8]   DEVELOPMENT AND EVALUATION OF A SYSTEM OF MICROENCAPSULATION OF PRIMARY RAT HEPATOCYTES [J].
CAI, ZH ;
SHI, ZQ ;
SHERMAN, M ;
SUN, AM .
HEPATOLOGY, 1989, 10 (05) :855-860
[9]   Clinical experience with a porcine hepatocyte-based liver support system [J].
Chen, SC ;
Hewitt, WR ;
Watanabe, FD ;
Eguchi, S ;
Kahaku, E ;
Middleton, Y ;
Rozga, J ;
Demetriou, AA .
INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS, 1996, 19 (11) :664-669
[10]  
CUNNINGHAM JM, 1992, INT J ARTIF ORGANS, V15, P162