Response of Human Liver Tissue to Innate Immune Stimuli

Wu, Xia; Roberto, Jessica B.; Knupp, Allison; Greninger, Alexander L.; Truong, Camtu D.; Hollingshead, Nicole; Kenerson, Heidi L.; Tuefferd, Marianne; Chen, L.-W. Antony; Koelle, David M.; Horton, Helen; Jerome, Keith R.; Polyak, Stephen J.; Yeung, Raymond S.

doi:10.3389/fimmu.2022.811551

Cited by 2 publications

(3 citation statements)

References 72 publications

(90 reference statements)

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“…They found that this resulted in long-term viability under standard cell culture conditions. This approach has since been employed in several other studies 9 , 27 , 49 . Enabling the use of standard culture conditions improves the practicality of the PCLS model given the ubiquity of cell culture incubators.…”

Section: Discussionmentioning

confidence: 99%

“…For a more clinically relevant model, PCLS can be collected from patient biopsies or from animal models after liver fibrosis or cirrhosis is induced in vivo. A variety of fibrosis etiologies have been investigated with this approach, including alcohol 26 , hepatitis infection 27 , non-alcoholic steatohepatitis (NASH) 26 , 28 , cholestasis 29 – 33 , and chemical hepatotoxins 26 , 34 , 35 .…”

Section: Introductionmentioning

confidence: 99%

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Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats

Leaker,

Wang,

Tam

et al. 2024

Sci Rep

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Precision-cut liver slices (PCLS) are increasingly used as a model to investigate anti-fibrotic therapies. However, many studies use PCLS from healthy animals treated with pro-fibrotic stimuli in culture, which reflects only the early stages of fibrosis. The effects of different culture conditions on PCLS from cirrhotic animals has not been well characterized and there is no consensus on optimal methods. In this study, we report a method for the collection and culture of cirrhotic PCLS and compare the effect of common culture conditions on viability, function, and gene expression. Additionally, we compared three methods of RNA isolation and identified a protocol with high yield and purity. We observed significantly increased albumin production when cultured with insulin-transferrin-selenium and dexamethasone, and when incubated on a rocking platform. Culturing with insulin-transferrin-selenium and dexamethasone maintained gene expression closer to the levels in fresh slices. However, despite stable viability and function up to 4 days, we found significant changes in expression of key genes by day 2. Interestingly, we also observed that cirrhotic PCLS maintain viability in culture longer than slices from healthy animals. Due to the influence of matrix stiffness on fibrosis and hepatocellular function, it is important to evaluate prospective anti-fibrotic therapies in a platform that preserves tissue biomechanics. PCLS from cirrhotic animals represent a promising tool for the development of treatments for chronic liver disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats

Leaker,

Wang,

Tam

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…For a more clinically relevant model, PCLS can be collected from patient biopsies or from animal models after liver fibrosis or cirrhosis is induced in vivo. A variety of fibrosis etiologies have been investigated with this approach, including alcohol 26 , hepatitis infection 27 , non-alcoholic steatohepatitis (NASH) 26,28 , cholestasis [29][30][31][32][33] , and chemical hepatotoxins 26,34,35 .…”

Section: Introductionmentioning

confidence: 99%

Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats

Leaker

Wang

Tam

et al. 2023

Preprint

View full text Add to dashboard Cite

Precision-cut liver slices (PCLS) are increasingly used as a model to investigate anti-fibrotic therapies. However, many studies use PCLS from healthy animals treated with pro-fibrotic stimuli in culture, which reflects only the early stages of fibrosis. The performance of PCLS from cirrhotic animals has not been well characterized and there is no consensus on optimal culture conditions. In this study, we report a method for the collection and culture of cirrhotic PCLS and compare the effect of common culture conditions on viability, function, and gene expression. Additionally, we compared three methods of RNA isolation and identified a protocol with high yield and purity. We observed significantly increased albumin production when cultured with insulin and dexamethasone, and when incubated on a rocking platform. Culturing with insulin and dexamethasone maintained gene expression closer to the levels in fresh slices. However, despite stable viability and function up to 4 days, we found significant changes in expression by day 2. Due to the influence of matrix stiffness on fibrosis and hepatocellular function, it is important to evaluate prospective anti-fibrotic therapies in a platform that preserves tissue biomechanics. PCLS from cirrhotic animals represent a promising tool for the development of treatments for chronic liver disease.

show abstract

Response of Human Liver Tissue to Innate Immune Stimuli

Cited by 2 publications

References 72 publications

Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats

Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats

Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats

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