Narrative review of in vitro experimental models of hepatic fibrogenesis

Chiabotto, Giulia; Ceccotti, Elena; Bruno, Stefania

doi:10.21037/dmr-21-102

Cited by 5 publications

(4 citation statements)

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“…These differences could be attributed to different cell culture conditions, which do not permit to maintain the quiescent state of HSCs for a long time. For instance, cultivation in low serum conditions (2%) should be preferable to preserve the quiescent state of LX-2, because higher serum conditions (10%) have been shown to induce the activated phenotype in LX-2 [64]. Besides, lacking the surrounding hepatic microenvironment, two-dimensional culture systems do not accurately reproduce the pathophysiological mechanisms of fibrogenesis and inflammation occurring in NASH [65].…”

Section: Discussionmentioning

confidence: 99%

Human liver stem cell-derived extracellular vesicles modulate long non-coding RNA expression profile in an in vivo model of non-alcoholic steatohepatitis

Chiabotto,

Ceccotti,

Pasquino

et al. 2023

Explor Dig Dis

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Aim: Modifications in long non-coding RNA (lncRNA) expression are associated with inflammation and fibrosis in chronic liver diseases. It has been recently demonstrated that human liver stem cells (HLSCs) and their extracellular vesicles (EVs) can effectively reduce inflammation and fibrosis in a murine model of non-alcoholic steatohepatitis (NASH). Now it has been evaluated whether EVs can modify the expression of inflammation-related lncRNAs in NASH liver. Methods: To induce NASH, severe combined immunodeficient mice were fed with a methionine-choline-deficient diet for 4 weeks. After 2 weeks of diet, 2.5 × 109 EVs were intravenously injected twice a week. An array of 84 inflammation-related lncRNAs was performed on the RNA isolated from NASH livers, and the expression of 14 selected lncRNAs was then validated by real-time polymerase chain reaction (PCR) analysis. Expression levels of maternally expressed gene 3 (Meg3) were further evaluated in vitro, in an activated human hepatic immortalized stellate cell line (LX-2) stimulated with EVs. Results: The screening showed an altered lncRNA expression profile in the liver of NASH mice, in respect to control healthy mice. EV treatment modulated several inflammation-related lncRNAs in NASH livers. Real-time PCR validation of array results indicated that EVs restored to normal levels the expression of 10 lncRNAs altered in NASH. In particular, EV stimulation reduced Meg3 expression levels, which were increased in NASH as well as in activated LX-2. Conclusions: HLSC-EVs regulate the expression of inflammation-related lncRNAs impaired in NASH livers and in an in vitro model of liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Human liver stem cell-derived extracellular vesicles modulate long non-coding RNA expression profile in an in vivo model of non-alcoholic steatohepatitis

Chiabotto,

Ceccotti,

Pasquino

et al. 2023

Explor Dig Dis

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Section: Employed Technologies and Methods For The 3d‐bioprinting Of ...mentioning

confidence: 99%

“…These cells directly derive from human primary stellate cells that spontaneously immortalized, and are particularly appreciated for their biologically relevant behavior, as well as for their ability to proliferate also at low serum concentrations. [75] The liver is also populated with hepatic sinusoidal endothelial cells. These cells are the building blocks of hepatic sinusoids, which constitute the hepatic vascular network.…”

Section: Cells For Liver Bioinksmentioning

confidence: 99%

Toward 3D‐Bioprinted Models of the Liver to Boost Drug Development

Guagliano

Volpini

Briatico‐Vangosa

et al. 2022

Macromolecular Bioscience

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The main problems in drug development are connected to enormous costs related to the paltry success rate. The current situation empowered the development of high-throughput and reliable instruments, in addition to the current golden standards, able to predict the failures in the early preclinical phase. Being hepatotoxicity responsible for the failure of 30% of clinical trials, and the 21% of withdrawal of marketed drugs, the development of complex in vitro models (CIVMs) of liver is currently one of the hottest topics in the field. Among the different fabrication techniques, 3D-bioprinting is emerging as a powerful ally for their production, allowing the manufacture of three-dimensional constructs characterized by computer-controlled and customized geometry, and inter-batches reproducibility. Thanks to these, it is possible to rapidly produce tailored cell-laden constructs, to be cultured within static and dynamic systems, thus reaching a further degree of personalization when designing in vitro models. This review highlights and prioritizes the most recent advances related to the development of CIVMs of the hepatic environment to be specifically applied to pharmaceutical research, with a special focus on 3D-bioprinting, since the liver is primarily involved in the metabolism of drugs.

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“…The liver, the largest internal organ of the body, plays a crucial role in numerous essential functions, including the control of homeostasis, metabolism, immunity, digestion, detoxification, and vitamin storage [1]. Liver fibrosis results from a variety of chronic insults, such as exposure to toxins or drugs, alcohol abuse, infections of parasitic or viral nature, cholestasis, as well as metabolic and genetic diseases [2]. With the success of therapies and vaccination strategies against hepatitis viruses, excessive nutrition has emerged as the primary contemporary threat to a healthy liver, making non-alcoholic fatty liver disease the most encountered hepatic disorder of the century [3].…”

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confidence: 99%