PMID- 35433753
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220507
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 9
DP  - 2022
TI  - Improved Precision-Cut Liver Slice Cultures for Testing Drug-Induced Liver 
      Fibrosis.
PG  - 862185
LID - 10.3389/fmed.2022.862185 [doi]
LID - 862185
AB  - In vitro models of human liver disease often fail to mimic the complex 3D 
      structures and cellular organizations found in vivo. Precision cut liver slices 
      (PCLS) retain the complex physiological architecture of the native liver and 
      therefore could be an exceptional in vitro liver model. However, the production 
      of PCLS induces a spontaneous culture-induced fibrogenic reaction, limiting the 
      application of PCLS to anti-fibrotic compounds. Our aim was to improve PCLS 
      cultures to allow compound-induced fibrosis induction. Hepatotoxicity in PCLS 
      cultures was analyzed by lactate dehydrogenase leakage and albumin secretion, 
      while fibrogenesis was analyzed by qRT-PCR and western blot for hepatic stellate 
      cell (HSC) activation markers and collagen 6 secretion by enzyme-linked 
      immunosorbent assays (ELISA). We demonstrate that supplementation of 3 mm mouse 
      PCLS cultures with valproate strongly reduces fibrosis and improves cell 
      viability in our PCLS cultures for up to 5 days. Fibrogenesis can still be 
      induced both directly and indirectly through exposure to TGFbeta and the hepatotoxin 
      acetaminophen, respectively. Finally, human PCLS cultures showed similar but less 
      robust results. In conclusion, we optimized PCLS cultures to allow for 
      drug-induced liver fibrosis modeling.
CI  - Copyright (c) 2022 Dewyse, De Smet, Verhulst, Eysackers, Kunda, Messaoudi, Reynaert 
      and van Grunsven.
FAU - Dewyse, Liza
AU  - Dewyse L
AD  - Department of Basic Biomedical Sciences, Liver Cell Biology Research Group, Vrije 
      Universiteit Brussel, Brussels, Belgium.
FAU - De Smet, Vincent
AU  - De Smet V
AD  - Department of Basic Biomedical Sciences, Liver Cell Biology Research Group, Vrije 
      Universiteit Brussel, Brussels, Belgium.
AD  - Department of Internal Medicine, Universitair Ziekenhuis Brussel, Brussels, 
      Belgium.
FAU - Verhulst, Stefaan
AU  - Verhulst S
AD  - Department of Basic Biomedical Sciences, Liver Cell Biology Research Group, Vrije 
      Universiteit Brussel, Brussels, Belgium.
FAU - Eysackers, Nathalie
AU  - Eysackers N
AD  - Department of Basic Biomedical Sciences, Liver Cell Biology Research Group, Vrije 
      Universiteit Brussel, Brussels, Belgium.
FAU - Kunda, Rastislav
AU  - Kunda R
AD  - Department of Surgery, Universitair Ziekenhuis Brussel, Brussels, Belgium.
FAU - Messaoudi, Nouredin
AU  - Messaoudi N
AD  - Department of Surgery, Universitair Ziekenhuis Brussel, Brussels, Belgium.
FAU - Reynaert, Hendrik
AU  - Reynaert H
AD  - Department of Basic Biomedical Sciences, Liver Cell Biology Research Group, Vrije 
      Universiteit Brussel, Brussels, Belgium.
AD  - Department of Gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, 
      Brussels, Belgium.
FAU - van Grunsven, Leo A
AU  - van Grunsven LA
AD  - Department of Basic Biomedical Sciences, Liver Cell Biology Research Group, Vrije 
      Universiteit Brussel, Brussels, Belgium.
LA  - eng
PT  - Journal Article
DEP - 20220330
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC9007724
OTO - NOTNLM
OT  - DILI
OT  - PCLS
OT  - VPA
OT  - hepatic stellate
OT  - human
OT  - in vitro
OT  - mouse
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/19 06:00
MHDA- 2022/04/19 06:01
PMCR- 2022/03/30
CRDT- 2022/04/18 06:39
PHST- 2022/01/25 00:00 [received]
PHST- 2022/03/04 00:00 [accepted]
PHST- 2022/04/18 06:39 [entrez]
PHST- 2022/04/19 06:00 [pubmed]
PHST- 2022/04/19 06:01 [medline]
PHST- 2022/03/30 00:00 [pmc-release]
AID - 10.3389/fmed.2022.862185 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2022 Mar 30;9:862185. doi: 10.3389/fmed.2022.862185. 
      eCollection 2022.