PMID- 38203321
OWN - NLM
STAT- MEDLINE
DCOM- 20240112
LR  - 20240113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 25
IP  - 1
DP  - 2023 Dec 21
TI  - Human Precision-Cut Liver Slices: A Potential Platform to Study Alcohol-Related 
      Liver Disease.
LID - 10.3390/ijms25010150 [doi]
LID - 150
AB  - Alcohol-related liver disease (ALD) encompasses a range of pathological 
      conditions that are complex to study at the clinical and preclinical levels. 
      Despite the global burden of ALD, there is a lack of effective treatments, and 
      mortality is high. One of the reasons for the unsuccessful development of novel 
      therapies is that experimental studies are hindered by the challenge of 
      recapitulating this multifactorial disorder in vitro, including the contributions 
      of hepatotoxicity, impaired lipid metabolism, fibrosis and inflammatory cytokine 
      storm, which are critical drivers in the pathogenesis of ALD in patients and 
      primary targets for drug development. Here, we present the unique characteristics 
      of the culture of human precision-cut liver slices (PCLS) to replicate key 
      disease processes in ALD. PCLS were prepared from human liver specimens and 
      treated with ethanol alone or in combination with fatty acids and 
      lipopolysaccharide (FA + LPS) for up to 5 days to induce hepatotoxic, 
      inflammatory and fibrotic events associated with ALD. Alcohol insult induced 
      hepatocyte death which was more pronounced with the addition of FA + LPS. This 
      mixture showed a significant increase in the cytokines conventionally associated 
      with the prototypical inflammatory response observed in severe ALD, and 
      interestingly, alcohol alone exhibited a different effect. Profibrogenic 
      activation was also observed in the slices and investigated in the context of 
      slice preparation. These results support the versatility of this organotypic 
      model to study different pathways involved in alcohol-induced liver damage and 
      ALD progression and highlight the applicability of the PCLS for drug discovery, 
      confirming their relevance as a bridge between preclinical and clinical studies.
FAU - Rastovic, Una
AU  - Rastovic U
AUID- ORCID: 0000-0003-1740-9067
AD  - The Roger Williams Institute of Hepatology, Foundation for Liver Research, London 
      SE5 9NT, UK.
AD  - Faculty of Life Sciences and Medicine, King's College London, London WC2R 2LS, 
      UK.
FAU - Bozzano, Sergio Francesco
AU  - Bozzano SF
AUID- ORCID: 0009-0000-7270-4611
AD  - The Roger Williams Institute of Hepatology, Foundation for Liver Research, London 
      SE5 9NT, UK.
AD  - Faculty of Life Sciences and Medicine, King's College London, London WC2R 2LS, 
      UK.
FAU - Riva, Antonio
AU  - Riva A
AUID- ORCID: 0000-0002-4974-2780
AD  - The Roger Williams Institute of Hepatology, Foundation for Liver Research, London 
      SE5 9NT, UK.
AD  - Faculty of Life Sciences and Medicine, King's College London, London WC2R 2LS, 
      UK.
FAU - Simoni-Nieves, Arturo
AU  - Simoni-Nieves A
AD  - The Roger Williams Institute of Hepatology, Foundation for Liver Research, London 
      SE5 9NT, UK.
AD  - Faculty of Life Sciences and Medicine, King's College London, London WC2R 2LS, 
      UK.
FAU - Harris, Nicola
AU  - Harris N
AUID- ORCID: 0000-0002-7396-5191
AD  - The Roger Williams Institute of Hepatology, Foundation for Liver Research, London 
      SE5 9NT, UK.
AD  - Faculty of Life Sciences and Medicine, King's College London, London WC2R 2LS, 
      UK.
FAU - Miquel, Rosa
AU  - Miquel R
AD  - Institute of Liver Studies, King's College London, London WC2R 2LS, UK.
FAU - Lackner, Carolin
AU  - Lackner C
AD  - Institute of Pathology, Medical University of Graz, 8010 Graz, Austria.
FAU - Zen, Yoh
AU  - Zen Y
AD  - Institute of Liver Studies, King's College London, London WC2R 2LS, UK.
FAU - Zamalloa, Ane
AU  - Zamalloa A
AD  - Institute of Liver Studies, King's College London, London WC2R 2LS, UK.
FAU - Menon, Krishna
AU  - Menon K
AD  - Institute of Liver Studies, King's College London, London WC2R 2LS, UK.
FAU - Heaton, Nigel
AU  - Heaton N
AD  - Institute of Liver Studies, King's College London, London WC2R 2LS, UK.
FAU - Chokshi, Shilpa
AU  - Chokshi S
AD  - The Roger Williams Institute of Hepatology, Foundation for Liver Research, London 
      SE5 9NT, UK.
AD  - Faculty of Life Sciences and Medicine, King's College London, London WC2R 2LS, 
      UK.
FAU - Palma, Elena
AU  - Palma E
AUID- ORCID: 0000-0001-6294-6676
AD  - The Roger Williams Institute of Hepatology, Foundation for Liver Research, London 
      SE5 9NT, UK.
AD  - Faculty of Life Sciences and Medicine, King's College London, London WC2R 2LS, 
      UK.
LA  - eng
GR  - N/a/Foundation for Liver Research/
PT  - Journal Article
DEP - 20231221
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Lipopolysaccharides)
RN  - 3K9958V90M (Ethanol)
RN  - 0 (Fatty Acids)
SB  - IM
MH  - Humans
MH  - *Lipopolysaccharides/toxicity
MH  - *Liver Diseases, Alcoholic
MH  - Hepatocytes
MH  - Ethanol/toxicity
MH  - Fatty Acids
PMC - PMC10778645
OTO - NOTNLM
OT  - alcoholic hepatitis
OT  - ethanol hepatotoxicity
OT  - ex vivo models
OT  - fibrosis
OT  - organotypic culture
COIS- The authors declare no conflicts of interest. The funders had no role in the 
      design of the study; in the collection, analyses or interpretation of data; in 
      the writing of the manuscript; or in the decision to publish the results.
EDAT- 2024/01/11 07:42
MHDA- 2024/01/12 06:43
PMCR- 2023/12/21
CRDT- 2024/01/11 01:17
PHST- 2023/07/20 00:00 [received]
PHST- 2023/12/15 00:00 [revised]
PHST- 2023/12/19 00:00 [accepted]
PHST- 2024/01/12 06:43 [medline]
PHST- 2024/01/11 07:42 [pubmed]
PHST- 2024/01/11 01:17 [entrez]
PHST- 2023/12/21 00:00 [pmc-release]
AID - ijms25010150 [pii]
AID - ijms-25-00150 [pii]
AID - 10.3390/ijms25010150 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Dec 21;25(1):150. doi: 10.3390/ijms25010150.