Liver cirrhosis: An overview of experimental models in rodents

Faccioli, Lanuza Alaby Pinheiro; Dias, Marlon Lemos; Paranhos, Bruno Andrade; Goldenberg, Regina Coeli dos Santos

doi:10.1016/j.lfs.2022.120615

Cited by 28 publications

(14 citation statements)

References 95 publications

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“…Many models can be selected, such as Wilson’s disease, 116 genetic or chemical induction of hepatocellular carcinoma, 117 fibrosis/cirrhosis, 118 – 120 ionizing radiation-induced lesion, 121 hepatic alcoholic steatosis, 122 among others. 115 Our group has shown success in the chemical-induced cirrhosis model by intraperitoneal administration of carbon tetrachloride (CCl 4 ). 119 , 123 – 125 However, other substances can be used to induce this pathological process.…”

Section: Animal Models To Test Ex Vivo Bioengineered Liver Functional...mentioning

confidence: 99%

Liver scaffolds obtained by decellularization: A transplant perspective in liver bioengineering

2022

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Liver transplantation is the only definitive treatment for many diseases that affect this organ, however, its quantity and viability are reduced. The study of liver scaffolds based on an extracellular matrix is a tissue bioengineering strategy with great application in regenerative medicine. Collectively, recent studies suggest that liver scaffold transplantation may assist in reestablishing hepatic function in preclinical diseased animals, which represents a great potential for application as a treatment for patients with liver disease in the future. This review focuses on useful strategies to promote liver scaffold transplantation and the main open questions about this context. We outline the current knowledge about ex vivo bioengineered liver transplantation, including the surgical techniques, recipient survival time, scaffold preparation before transplantation, and liver disease models. We also highlight the current limitations and future directions regarding in vivo bioengineering techniques.

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Section: Animal Models To Test Ex Vivo Bioengineered Liver Functional...mentioning

confidence: 99%

Liver scaffolds obtained by decellularization: A transplant perspective in liver bioengineering

2022

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“…However, both pathogenic and suppression properties of intrahepatic CD8 + T cells have been highlighted in liver fibrosis/cirrhosis progression [61], and the functional and phenotypical characteristics of the CD8 + T cells associated with positive benefit in the liver disease are largely unknown. Albillos et al [20] used murine diet-induced nonalcoholic steatohepatitis model (NASH) [2], a currently the leading cause of chronic liver disease worldwide [62], and mainly characterized lobular inflammation and hepatocyte ballooning [63], demonstrating a direct role of CD8 + T cells in fibrosis resolution by promoting HSC apoptosis in a CCR5-dependent manner [63], primarily highlighting the undefined role of liver-resident CD8 + T cells in the fibrotic/cirrhotic liver niche.…”

Section: The 0014% Den-treated Liver Fibrosis/cirrhosis Mouse Model-a...mentioning

confidence: 99%

“…The healthy liver performs over 500 different functions to maintain its homeostasis [1,2], and any assault could not only impact the architecture of hepatic cells [3] but also injure niche cells, like inflammatory and immune cells such as CD8-positive cytotoxic T lymphocyte subset (CD8 + T cells) which have been recently highlighted [4]. Liver cirrhosis is an end-stage liver disease (ESLD) and a major cause of morbidity and mortality globally [5].…”

Section: Introductionmentioning

confidence: 99%

Survival Fate of Hepatic Stem/Progenitor and Immune Cells in a Liver Fibrosis/Cirrhosis Animal Model and Clinical Implications

Yan¹,

Hu²,

Wu³

et al. 2023

Animal Models and Experimental Research in Medicine

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This chapter provides novel information about the survival features of hepatic resident stem/progenitor cells (NG2+ HSPs) during liver fibrosis/cirrhotic development. A well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhotic/cancer mouse model was developed to evaluate the fate of the HSPs and its clinical implications. This model possess three time-zones during the disease development: fibrosis (3–5 weeks post-DEN), cirrhosis (6–10 weeks post-DEN), and cancers (up to 10 weeks post-DEN). During this process, the model represents histological patterns similar to those described in humans and shows better survival of the HSPs in the fibrotic zone, which was correlated with inflammatory signals, as compared to the cirrhotic zone. It has also been discovered that immune CD8+ T cells in the fibrotic zone are beneficial in liver fibrosis resolution, suggesting that the fibrotic time zone is important for mobilizing endogenous HSPs and cell-based therapy. As such, we hypothesize that clinical strategies in fibrotic/cirrhotic liver treatment are necessary either in time at the fibrotic phase or to adopt an approach of regulating HSP viability when the disease develops into the cirrhotic phase.

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“…Upon termination, the mice were sacrificed and blood was collected by cardiac punctuation, followed by perfusion with 30 mL of PBS. The livers were dissected and divided into two parts; one part was immediately frozen in dry ice for biochemical analyses, and the other part was fixed in paraformaldehyde for histological studies [10].…”

Section: Ccl4 Induced Liver Damagementioning

confidence: 99%

Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model

Cheng

Jia

Zhang

et al. 2022

Cells

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Heparanase is elevated in various pathological conditions, primarily cancer and inflammation. To investigate the significance and involvement of heparanase in liver fibrosis, we compared the susceptibility of wild-type (WT) and heparanase-overexpressing transgenic (Hpa-tg) mice to carbon tetrachloride (CCL4)-induced fibrosis. In comparison with WT mice, Hpa-tg mice displayed a severe degree of tissue damage and fibrosis, including higher necrotic tendency and intensified expression of smooth muscle actin. While damage to the WT liver started to recover after the acute phase, damage to the Hpa-tg liver was persistent. Recovery was attributed, in part, to heparanase-stimulated autophagic activity in response to CCL4, leading to increased apoptosis and necrosis. The total number of stellate cells was significantly higher in the Hpa-tg than the WT liver, likely contributing to the increased amounts of lipid droplets and smooth muscle actin. Our results support the notion that heparanase enhances inflammatory responses, and hence may serve as a target for the treatment of liver damage and fibrosis.

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Liver cirrhosis: An overview of experimental models in rodents

Cited by 28 publications

References 95 publications

Liver scaffolds obtained by decellularization: A transplant perspective in liver bioengineering

Liver scaffolds obtained by decellularization: A transplant perspective in liver bioengineering

Survival Fate of Hepatic Stem/Progenitor and Immune Cells in a Liver Fibrosis/Cirrhosis Animal Model and Clinical Implications

Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model

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