A transcriptomic study suggesting human iPSC-derived hepatocytes potentially offer a better in vitro model of hepatotoxicity than most hepatoma cell lines

Gao, Xiugong; Liu, Yitong

doi:10.1007/s10565-017-9383-z

Cited by 62 publications

(40 citation statements)

References 47 publications

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“…Though immortalized human cell lines, such as HUH7 and HepG2, as well as iPSC-derived hepatocytes, can be induced towards a steatotic phenotype in culture, multiple studies have shown that these cells poorly represent the native liver metabolic function, thus keeping primary human hepatocytes as the gold standard for in vitro studies [20–22]. In addition to hepatocytes, the addition of non-parenchymal cells (NPC), including human hepatic stellate cells (HSCs), resident inflammatory cells (e.g., Kupffer cells, macrophages), and/or sinusoidal endothelial cells (sECs), affect liver biology and are known to contribute to the progression of NAFLD [23–25].…”

Section: Human In Vitro Organotypic Models Of Nafldmentioning

confidence: 99%

Translating scientific discovery: the need for preclinical models of nonalcoholic steatohepatitis

et al. 2018

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Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world, affecting about 1/3 of the US general population and remaining as a significant cause of morbidity and mortality. The hallmark of the disease is the excessive accumulation of fat within the liver cells (hepatocytes), which eventually paves the way to cellular stress, injury and apoptosis. NAFLD is strongly associated with components of the metabolic syndrome and is fast emerging as a leading cause of liver transplant in the USA. Based on clinico-pathologic classification, NAFLD may present as isolated lipid collection (steatosis) within the hepatocytes (referred to as non-alcoholic fatty liver; NAFL); or as the more aggressive phenotype (known as non-alcoholic steatohepatitis; NASH). There are currently no regulatory agency-approved medication for NAFLD, despite the enormous work and resources that have gone into the study of this condition. Therefore, there remains a huge unmet need in developing and utilizing pre-clinical models that will recapitulate the disease condition in humans. In line with progress being made in developing appropriate disease models, this review highlights the cutting-edge preclinical in vitro and animal models that try to recapitulate the human disease pathophysiology and/or clinical manifestations.

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Section: Human In Vitro Organotypic Models Of Nafldmentioning

confidence: 99%

Translating scientific discovery: the need for preclinical models of nonalcoholic steatohepatitis

et al. 2018

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“…This may be a reason for the disappointing outcomes of the clinical ELAD trials. Another cell source comprises original or induced stem cells, which, however, display a limited functional spectrum as well [17,24]. To date, the most functional human liver cell line is the HepaRG cell line [25], which further differentiates by culturing in the AMC-BAL system [26].…”

Section: Concluding Remarks Clinically Applied Cell-based Alssmentioning

confidence: 99%

“…To date, the most functional human liver cell line is the HepaRG cell line [25], which further differentiates by culturing in the AMC-BAL system [26]. Comparison of the transcriptomes of different proliferative sources of human liver cells showed that HepaRG cells most closely resembled primary human hepatocytes [24,27]. Further improvement of existing cell systems may be achieved by (conditional) ectopic expression of limiting regulatory or structural genes and by application of cell culture systems promoting maturation, e.g.…”

Section: Concluding Remarks Clinically Applied Cell-based Alssmentioning

confidence: 99%

End-stage liver failure: filling the treatment gap at the intensive care unit

Chamuleau

Hoekstra

2019

J Artif Organs

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End-stage liver failure is a condition of collapsing liver function with mortality rates up to 80. Liver transplantation is the only lifesaving therapy. There is an unmet need for therapy to extend the waiting time for liver transplantation or regeneration of the native liver. Here we review the state-of-the-art of non-cell based and cell-based artificial liver support systems, cell transplantation and plasma exchange, with the first therapy relying on detoxification, while the others aim to correct also other failing liver functions and/or modulate the immune response. Meta-analyses on the effect of non-cell based systems show contradictory outcomes for different types of albumin purification devices. For bioartificial livers proof of concept has been shown in animals with liver failure. However, large clinical trials with two different systems did not show a survival benefit. Two clinical trials with plasma exchange and one with transplantation of mesenchymal stem cells showed positive outcomes on survival. Detoxification therapies lack adequacy for most patients. Correction of additional liver functions, and also modulation of the immune system hold promise for future therapy of liver failure.

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“…This can provide guidance for researchers in the diverse areas of toxicology research that are interested in applying these new technologies to their own work. Encouragingly, research-based articles also being published in CBT, for example, the application of iPSC and cell reprogramming strategies for predicting drug toxicity Gao and Liu 2017). If CBT can continue to expand its scope to encompass cutting edge technologies, while still providing a highquality resource for toxicology research, we believe the journal can continue to expand and publish high quality research and reviews.…”

Section: Summary and Opinionmentioning

confidence: 99%