Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies

被引:302
作者
de Graaf, Inge A. M. [1 ]
Olinga, Peter [1 ]
de Jager, Marina H. [1 ]
Merema, Marjolijn T. [1 ]
de Kanter, Ruben [1 ]
van de Kerkhof, Esther G. [1 ]
Groothuis, Geny M. M. [1 ]
机构
[1] Univ Groningen, Groningen Res Inst Pharm, Dept Pharm, Div Pharmacokinet Toxicol & Targeting, Groningen, Netherlands
关键词
IN-VITRO MODEL; POLYCYCLIC AROMATIC-HYDROCARBONS; DYNAMIC ORGAN-CULTURE; ANTI-FIBROTIC DRUGS; RAT-LIVER; TISSUE-SLICES; ISCHEMIA-REPERFUSION; ISOLATED HEPATOCYTES; MANNOSE; 6-PHOSPHATE; COLLAGEN SANDWICH;
D O I
10.1038/nprot.2010.111
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Precision-cut tissue slices (PCTS) are viable ex vivo explants of tissue with a reproducible, well defined thickness. They represent a mini-model of the organ under study and contain all cells of the tissue in their natural environment, leaving intercellular and cell-matrix interactions intact, and are therefore highly appropriate for studying multicellular processes. PCTS are mainly used to study the metabolism and toxicity of xenobiotics, but they are suitable for many other purposes. Here we describe the protocols to prepare and incubate rat and human liver and intestinal slices. Slices are prepared from fresh liver by making a cylindrical core using a drill with a hollow bit, from which slices are cut with a specially designed tissue slicer. Intestinal tissue is embedded in cylinders of agarose before slicing. Slices remain viable for 24 h (intestine) and up to 96 h (liver) when incubated in 6- or 12-well plates under 95% O-2/5% CO2 atmosphere.
引用
收藏
页码:1540 / 1551
页数:12
相关论文
共 107 条
[21]  
de Kanter Ruben, 2005, Journal of Pharmacological and Toxicological Methods, V51, P65, DOI 10.1016/j.vascn.2004.07.007
[22]   Induction of metabolism and transport in human intestine: Validation of precision-cut slices as a tool to study induction of drug metabolism in human intestine in vitro [J].
De Kerkhof, Esther G. Van ;
De Graaf, Inge A. M. ;
Ungell, Anna-Lena B. ;
Groothuis, Geny M. M. .
DRUG METABOLISM AND DISPOSITION, 2008, 36 (03) :604-613
[23]  
deKanter R, 1997, DEV AN VET, V27, P851
[24]   Time- and concentration-dependent induction of CYP1A1 and CYP1A2 in precision-cut rat liver slices incubated in dynamic organ culture in the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin [J].
Drahushuk, AT ;
McGarrigle, BP ;
Slezak, BP ;
Stegeman, JJ ;
Olson, JR .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1999, 155 (02) :127-138
[25]   HEPATOCYTES IN COLLAGEN SANDWICH - EVIDENCE FOR TRANSCRIPTIONAL AND TRANSLATIONAL REGULATION [J].
DUNN, JCY ;
TOMPKINS, RG ;
YARMUSH, ML .
JOURNAL OF CELL BIOLOGY, 1992, 116 (04) :1043-1053
[26]   Microarray analysis in rat liver slices correctly predicts in vivo hepatotoxicity [J].
Elferink, M. G. L. ;
Olinga, P. ;
Draaisma, A. L. ;
Merema, M. T. ;
Bauerschmidt, S. ;
Polman, J. ;
Schoonen, W. G. ;
Groothuis, G. M. M. .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2008, 229 (03) :300-309
[27]   LPS-induced downregulation of MRP2 and BSEP in human liver is due to a posttranscriptional process [J].
Elferink, MGL ;
Olinga, P ;
Draaisma, AL ;
Merema, MT ;
Faber, KN ;
Slooff, MJH ;
Meijer, DKF ;
Groothuis, GMM .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2004, 287 (05) :G1008-G1016
[28]   COMPARATIVE METABOLISM AND TOXICITY OF DICHLOROBENZENES IN SPRAGUE-DAWLEY, FISCHER-344 AND HUMAN LIVER SLICES [J].
FISHER, RL ;
HASAL, SJ ;
SIPES, IG ;
GANDOLFI, AJ ;
BRENDEL, K .
HUMAN & EXPERIMENTAL TOXICOLOGY, 1995, 14 (05) :414-421
[29]   COLDPRESERVATION AND CRYOPRESERVATION OF HUMAN LIVER AND KIDNEY SLICES [J].
FISHER, RL ;
HASAL, SJ ;
SANUIK, JT ;
SCOTT, KS ;
GANDOLFI, AJ ;
BRENDEL, K .
CRYOBIOLOGY, 1993, 30 (03) :250-261
[30]   Human liver quality is a dominant factor in the outcome of in vitro studies [J].
Fisher, RL ;
Gandolfi, AJ ;
Brendel, K .
CELL BIOLOGY AND TOXICOLOGY, 2001, 17 (03) :179-189