PMID- 26514934
OWN - NLM
STAT- MEDLINE
DCOM- 20161007
LR  - 20181202
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 30
IP  - 1 Pt B
DP  - 2015 Dec 25
TI  - Viability, function and morphological integrity of precision-cut liver slices 
      during prolonged incubation: Effects of culture medium.
PG  - 288-99
LID - S0887-2333(15)00267-2 [pii]
LID - 10.1016/j.tiv.2015.10.008 [doi]
AB  - Precision-cut liver slices (PCLS) are an ex vivo model for metabolism and 
      toxicity studies. However, data on the maintenance of the morphological integrity 
      of the various cell types in the slices during prolonged incubation are lacking. 
      Therefore, our aims were to characterize morphological and functional changes in 
      rat PCLS during five days of incubation in a rich medium, RegeneMed(R), and a 
      standard medium, Williams' Medium E. Although cells of all types in the slices 
      remain viable, profound changes in morphology were observed, which were more 
      prominent in RegeneMed(R). Slices underwent notable fibrosis, bile duct 
      proliferation and fat deposition. Slice thickness increased, resulting in 
      necrotic areas, while slice diameter decreased, possibly indicating cell 
      migration. An increased proliferation of parenchymal and non-parenchymal cells 
      (NPCs) was observed. Glycogen, albumin and Cyp3a1 were maintained albeit to a 
      different level in two media. In conclusion, both hepatocytes and NPCs remain 
      viable and functional, enabling five-day toxicity studies. Tissue remodeling and 
      formation of a new capsule-like cell lining around the slices are evident after 
      3-4 days. The differences in effects between media emphasize the importance of 
      media selection and of the recognition of morphological changes in PCLS, when 
      interpreting results from toxicological or pharmacological studies.
FAU - Starokozhko, Viktoriia
AU  - Starokozhko V
AD  - Division of Pharmacokinetics, Toxicology and Targeting, Groningen Research 
      Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV 
      Groningen, The Netherlands.
FAU - Abza, Getahun B
AU  - Abza GB
AD  - Division of Pharmacokinetics, Toxicology and Targeting, Groningen Research 
      Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV 
      Groningen, The Netherlands.
FAU - Maessen, Hedy C
AU  - Maessen HC
AD  - Division of Pharmacokinetics, Toxicology and Targeting, Groningen Research 
      Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV 
      Groningen, The Netherlands.
FAU - Merema, Marjolijn T
AU  - Merema MT
AD  - Division of Pharmacokinetics, Toxicology and Targeting, Groningen Research 
      Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV 
      Groningen, The Netherlands.
FAU - Kuper, Frieke
AU  - Kuper F
AD  - TNO, Utrechtseweg 48, 3704 HE Zeist, The Netherlands.
FAU - Groothuis, Geny M M
AU  - Groothuis GM
AD  - Division of Pharmacokinetics, Toxicology and Targeting, Groningen Research 
      Institute for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV 
      Groningen, The Netherlands. Electronic address: g.m.m.groothuis@rug.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151026
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Culture Media)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
SB  - IM
MH  - Adenosine Triphosphate/analysis
MH  - Animals
MH  - Cell Proliferation
MH  - Culture Media
MH  - Homeostasis
MH  - In Vitro Techniques
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Lipid Metabolism
MH  - Liver/pathology/*physiology
MH  - Male
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Precision-cut liver slices
OT  - Prolonged incubation
EDAT- 2015/10/31 06:00
MHDA- 2016/10/08 06:00
CRDT- 2015/10/31 06:00
PHST- 2015/09/10 00:00 [received]
PHST- 2015/10/20 00:00 [revised]
PHST- 2015/10/24 00:00 [accepted]
PHST- 2015/10/31 06:00 [entrez]
PHST- 2015/10/31 06:00 [pubmed]
PHST- 2016/10/08 06:00 [medline]
AID - S0887-2333(15)00267-2 [pii]
AID - 10.1016/j.tiv.2015.10.008 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2015 Dec 25;30(1 Pt B):288-99. doi: 10.1016/j.tiv.2015.10.008. 
      Epub 2015 Oct 26.