Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes

Baxter, M.; Withey, Sarah; Harrison, Sean; Segeritz, Charis-Patricia; Zhang, Fang; Atkinson-Dell, Rebecca; Rowe, Cliff; Gerrard, Dave T.; Sison-Young, Rowena; Jenkins, Roz; Henry, Joanne; Berry, Andrew; Mohamet, Lisa; Best, Marie; Fenwick, Stephen; Malik, Hassan; Kitteringham, Neil R.; Goldring, Chris; Hanley, Karen Piper; Vallier, Ludovic; Hanley, Neil A.

doi:10.1016/j.jhep.2014.10.016

Cited by 293 publications

(279 citation statements)

References 37 publications

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“…Although these protocols generated pancreatic progenitors, the differentiated endocrine cells tended to produce both glucagon and insulin. This has been taken as a sign of immaturity, as has also been noted for other foregut endoderm derivatives (Baxter et al, 2015). Indeed, Melton and colleagues identified transcriptional similarities between PSC-derived β-cells and human fetal β-cells, which may explain a relative lack of glucose responsiveness (Hrvatin et al, 2014).…”

Section: Mapping Human Psc Differentiation Onto Human Pancreas Develomentioning

confidence: 82%

Human pancreas development

et al. 2015

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A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

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Section: Mapping Human Psc Differentiation Onto Human Pancreas Develomentioning

confidence: 82%

Human pancreas development

et al. 2015

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“…109,111,112 Although various modifications of cytokine concentration, application periods, and combinations were investigated, all of the protocols so far show that the hepatocyte-like cells (HLC) obtained still show an immature phenotype with reduced hepatic functionality when compared to PHH. 113,114 Approaches for the improvement of hepatic maturation.…”

Section: Human Pluripotent Stem Cellsmentioning

confidence: 99%

“…optimized versus previous method), 118,121,127 hepatic cell lines 112 and PHH from fetal or adult origin, cultured or freshly isolated. 113,114 It is essential that differentiation protocols are highly reproducible for in vitro pharmacological and toxicity studies. Most of the current differentiation protocols apply defined serum-free culture media with recombinant growth factors.…”

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confidence: 99%

Cell sources forin vitrohuman liver cell culture models

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et al. 2016

Exp Biol Med (Maywood)

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In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro. However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro. Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described.

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“…At present, the state-of-the-art hepatic differentiation protocols produce cells, which are foetal in both phenotype and function (66). There remains insufficient data demonstrating that iPSC-derived hepatocyte-like cells are comparable to existing primary hepatocyte systems or hepatic cell lines, although improved protocols for generating hepatocytes are progressing rapidly.…”

Section: Discussionmentioning

confidence: 99%

Pluripotent stem cells to hepatocytes, the journey so far

2017

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Abstract. Over the past several years, there has been substantial progress in the field of regenerative medicine, which has enabled new possibilities for research and clinical application. For example, there are ongoing efforts directed at generating functional hepatocytes from adult-derived pluripotent cells for toxicity screening, generating disease models or, in the longer term, for the treatment of liver failure. In the present review, the authors summarise recent developments in regenerative medicine and pluripotent stem cells, the methods and tissues used for reprogramming and the differentiation of induced pluripotent stem cells (iPSCs) into hepatocyte-like cells. In addition, the hepatic disease models developed using iPSC technologies are discussed, as well as the potential for gene editing.

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Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes

Abstract: Graphical abstract

Cited by 293 publications

References 37 publications

Human pancreas development

Human pancreas development

Cell sources forin vitrohuman liver cell culture models

Pluripotent stem cells to hepatocytes, the journey so far

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