Maintenance of organized adult liver tissue in vitro

1962 ◽  
Vol 28 (2) ◽  
pp. 370-380 ◽  
Author(s):  
R.L. Ingram
Keyword(s):  
Liver Tissue ◽  
Adult Liver

scholarly journals Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads

2021 ◽  
Vol 220 (10) ◽  
Author(s):  
Lenka Belicova ◽  
Urska Repnik ◽  
Julien Delpierre ◽  
Elzbieta Gralinska ◽  
Sarah Seifert ◽  
...  
Keyword(s):  
Liver Tissue ◽  
Cyst Formation ◽  
Apical Surface ◽  
Adult Liver ◽  
3D Network ◽  
Anisotropic Expansion ◽  
Tubular Lumen ◽  
Hepatocyte Polarity ◽  
Mechanical Elements

Lumen morphogenesis results from the interplay between molecular pathways and mechanical forces. In several organs, epithelial cells share their apical surfaces to form a tubular lumen. In the liver, however, hepatocytes share the apical surface only between adjacent cells and form narrow lumina that grow anisotropically, generating a 3D network of bile canaliculi (BC). Here, by studying lumenogenesis in differentiating mouse hepatoblasts in vitro, we discovered that adjacent hepatocytes assemble a pattern of specific extensions of the apical membrane traversing the lumen and ensuring its anisotropic expansion. These previously unrecognized structures form a pattern, reminiscent of the bulkheads of boats, also present in the developing and adult liver. Silencing of Rab35 resulted in loss of apical bulkheads and lumen anisotropy, leading to cyst formation. Strikingly, we could reengineer hepatocyte polarity in embryonic liver tissue, converting BC into epithelial tubes. Our results suggest that apical bulkheads are cell-intrinsic anisotropic mechanical elements that determine the elongation of BC during liver tissue morphogenesis.

scholarly journals Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bioactivation and detoxification

2021 ◽  
Author(s):  
Lawrence Howell ◽  
Rosalind E. Jenkins ◽  
Stephen Lynch ◽  
Carrie Duckworth ◽  
B. Kevin Park ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Rna Polymerase Ii ◽  
Liver Tissue ◽  
Drug Disposition ◽  
Multiple Drug ◽  
Proteomic Profiling ◽  
Cytochrome P450 3A ◽  
Drug Induced

AbstractHepatic organoids are a recent innovation in in vitro modeling. Initial studies suggest that organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, their potential for drug metabolism and detoxification remains poorly characterized, and their global proteome has yet to be compared to their tissue of origin. This analysis is urgently needed to determine what gain-of-function this new model may represent for modeling the physiological and toxicological response of the liver to xenobiotics. Global proteomic profiling of undifferentiated and differentiated hepatic murine organoids and donor-matched livers was, therefore, performed to assess both their similarity to liver tissue, and the expression of drug-metabolizing enzymes and transporters. This analysis quantified 4405 proteins across all sample types. Data are available via ProteomeXchange (PXD017986). Differentiation of organoids significantly increased the expression of multiple cytochrome P450, phase II enzymes, liver biomarkers and hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, the organoids contain multiple drug metabolizing and transporter proteins necessary for liver function and drug metabolism, such as cytochrome P450 3A, glutathione-S-transferase alpha and multidrug resistance protein 1A. Indeed, the differentiated organoids were shown to exhibit increased sensitivity to midazolam (10–1000 µM) and irinotecan (1–100 µM), when compared to the undifferentiated organoids. The predicted reduced activity of HNF4A and a resulting dysregulation of RNA polymerase II may explain the partial differentiation of the organoids. Although further experimentation, optimization and characterization is needed relative to pre-existing models to fully contextualize their use as an in vitro model of drug-induced liver injury, hepatic organoids represent an attractive novel model of the response of the liver to xenobiotics. The current study also highlights the utility of global proteomic analyses for rapid and accurate evaluation of organoid-based test systems.

Characterization of in vitro healthy and pathological human liver tissue periodicity using backscattered ultrasound signals

2006 ◽  
Vol 32 (5) ◽  
pp. 649-657 ◽  
Author(s):  
Christiano Bittencourt Machado ◽  
Wagner Coelho de Albuquerque Pereira ◽  
Mahmoud Meziri ◽  
Pascal Laugier
Keyword(s):  
Liver Tissue ◽  
Human Liver ◽  
Human Liver Tissue ◽  
Ultrasound Signals

scholarly journals The Hepatitis C Virus-Induced Membranous Web in Liver Tissue

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 191
Author(s):  
Emmanuelle Blanchard ◽  
Philippe Roingeard
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Innate Immune Response ◽  
Liver Tissue ◽  
Hepatoma Cell ◽  
Membrane Vesicles ◽  
Innate Immune ◽  
Host Cell Membrane

Host cell membrane rearrangements induced by the hepatitis C virus (HCV) have been exclusively studied in vitro. These studies have shown that HCV induces double-membrane vesicles (DMVs), which probably serve to separate replication sites from the cytoplasmic sensors of the innate immune response. We report for the first time the observation of HCV-induced membrane rearrangements in liver biopsy specimens from patients chronically infected with HCV. Unlike observations performed in vitro, the membranous web detected in liver tissue seems essentially made of clusters of single-membrane vesicles derived from the endoplasmic reticulum and close to lipid droplets. This suggests that the DMVs could be a hallmark of laboratory-adapted HCV strains, possibly due to their ability to achieve a high level of replication. Alternatively, the concealment of viral RNA in DMVs may be part of innate immune response mechanisms particularly developed in hepatoma cell lines cultured in vitro. In any case, this constitutes the first report showing the differences in the membranous web established by HCV in vitro and in vivo.

scholarly journals Expression of the Metalloproteinase ADAM8 Is Upregulated in Liver Inflammation Models and Enhances Cytokine Release In Vitro

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Tanzeela Awan ◽  
Aaron Babendreyer ◽  
Justyna Wozniak ◽  
Abid Mahmood Alvi ◽  
Viktor Sterzer ◽  
...  
Keyword(s):  
Cell Lines ◽  
Inflammatory Mediators ◽  
Liver Tissue ◽  
Stellate Cell ◽  
Hepatoma Cell ◽  
Cell Types ◽  
Chronic Liver ◽  
Liver Inflammation ◽  
Tnf Α

Acute and chronic liver inflammation is driven by cytokine and chemokine release from various cell types in the liver. Here, we report that the induction of inflammatory mediators is associated with a yet undescribed upregulation of the metalloproteinase ADAM8 in different murine hepatitis models. We further show the importance of ADAM8 expression for the production of inflammatory mediators in cultured liver cells. As a model of acute inflammation, we investigated liver tissue from lipopolysaccharide- (LPS-) treated mice in which ADAM8 expression was markedly upregulated compared to control mice. In vitro, stimulation with LPS enhanced ADAM8 expression in murine and human endothelial and hepatoma cell lines as well as in primary murine hepatocytes. The enhanced ADAM8 expression was associated with an upregulation of TNF-α and IL-6 expression and release. Inhibition studies indicate that the cytokine response of hepatoma cells to LPS depends on the activity of ADAM8 and that signalling by TNF-α can contribute to these ADAM8-dependent effects. The role of ADAM8 was further confirmed with primary hepatocytes from ADAM8 knockout mice in which TNF-α and IL-6 induction and release were considerably attenuated. As a model of chronic liver injury, we studied liver tissue from mice undergoing high-fat diet-induced steatohepatitis and again observed upregulation of ADAM8 mRNA expression compared to healthy controls. In vitro, ADAM8 expression was upregulated in hepatoma, endothelial, and stellate cell lines by various mediators of steatohepatitis including fatty acid (linoleic-oleic acid), IL-1β, TNF-α, IFN-γ, and TGF-β. Upregulation of ADAM8 was associated with the induction and release of proinflammatory cytokines (TNF-α and IL-6) and chemokines (CX3CL1). Finally, knockdown of ADAM8 expression in all tested cell types attenuated the release of these mediators. Thus, ADAM8 is upregulated in acute and chronic liver inflammation and is able to promote inflammation by enhancing expression and release of inflammatory mediators.

Effect of Prolonged Consumption of Pemmican Survival Ration on Some Aspects of the Intermediary Metabolism of Rat Liver Tissue

1958 ◽  
Vol 193 (2) ◽  
pp. 449-454 ◽  
Author(s):  
John P. Hannon ◽  
David A. Vaughan
Keyword(s):  
Cytochrome C ◽  
Respiratory Rate ◽  
Rat Liver ◽  
Liver Tissue ◽  
In Vitro Metabolism ◽  
Intermediary Metabolism ◽  
Normal Value ◽  
Endogenous Metabolism ◽  
Prolonged Feeding

The effect of prolonged feeding (3–5 months) of pemmican on some aspects of the in vitro metabolism of liver tissue was investigated. The endogenous metabolism of liver slices and homogenates was significantly increased by pemmican, probably due to an increase in the amount of readily metabolizable substrate. Utilizing mitochondrial preparations, it was found that with all substrates studied, except glutamate, α-ketoglutarate and succinate, the respiratory rate was not affected by the previous diet in the absence of added cytochrome c and diphosphopyridine nucleotide. The three substrates mentioned were oxidized at significantly lower rates in the pemmican group. Upon the addition of cytochrome c and diphosphopyridine nucleotide the qo2 of glutamate, α-ketoglutarate, and succinate was returned to the normal value.

scholarly journals Hydrogels for Liver Tissue Engineering

2019 ◽  
Vol 6 (3) ◽  
pp. 59 ◽  
Author(s):  
Shicheng Ye ◽  
Jochem W.B. Boeter ◽  
Louis C. Penning ◽  
Bart Spee ◽  
Kerstin Schneeberger
Keyword(s):  
Tissue Engineering ◽  
Liver Tissue ◽  
Drug Testing ◽  
In Vitro Models ◽  
Liver Tissue Engineering ◽  
Synthetic Materials ◽  
Toxicological Studies ◽  
End Stage

Bioengineered livers are promising in vitro models for drug testing, toxicological studies, and as disease models, and might in the future be an alternative for donor organs to treat end-stage liver diseases. Liver tissue engineering (LTE) aims to construct liver models that are physiologically relevant. To make bioengineered livers, the two most important ingredients are hepatic cells and supportive materials such as hydrogels. In the past decades, dozens of hydrogels have been developed to act as supportive materials, and some have been used for in vitro models and formed functional liver constructs. However, currently none of the used hydrogels are suitable for in vivo transplantation. Here, the histology of the human liver and its relationship with LTE is introduced. After that, significant characteristics of hydrogels are described focusing on LTE. Then, both natural and synthetic materials utilized in hydrogels for LTE are reviewed individually. Finally, a conclusion is drawn on a comparison of the different hydrogels and their characteristics and ideal hydrogels are proposed to promote LTE.

Sign in / Sign up

Export Citation Format

Share Document