Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells

Godoy, Paulo R. D. V.; Schmidt‐Heck, Wolfgang; Natarajan, Krishnamurthy; Lucendo‐Villarin, Baltasar; Szkolnika, D.; Asplund, Annika; Björquist, Petter; Widera, Agata; Stoeber, Regina; Campos, Gisela; Hammad, Seddik; Sachinidis, Agapios; Damm, Georg; Weiss, Thomas S.; Nüssler, A; Synnergren, Jane; Edlund, Karolina; Küppers-Munther, Barbara; Hengstler, JG

doi:10.1016/j.toxlet.2015.08.545

Cited by 32 publications

(62 citation statements)

References 26 publications

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“…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

Zeilinger

Freyer

Damm

et al. 2016

Exp Biol Med (Maywood)

179

160

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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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mentioning

confidence: 99%

Cell sources forin vitrohuman liver cell culture models

Zeilinger

Freyer

Damm

et al. 2016

Exp Biol Med (Maywood)

179

160

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“…Hepatic differentiation protocols, evaluation strategies and phenotypic or functional outcomes vary widely between different laboratories (50). A direct comparison of the efficiency of pluripotent stem cell lines to generate functional hepatocytes is therefore difficult.…”

Section: Generating Hepatocytes From Ips Cellsmentioning

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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“…Publications by various other research groups have utilized Human Protein Atlas information for determination of tissue specificity across the large set of normal tissues, in order to elucidate the nature of the analyzed proteins [11,12]. The thorough exploration of protein expression using highthroughput immunohistochemical staining in a tissue microarray format provides a detailed map of where a particular protein is expressed, in contrast to many publications analyzing only a few organs.…”

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confidence: 99%

The Human Protein Atlas – an important resource for basic and clinical research

Lindskog

2016

Expert Review of Proteomics

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Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells

Cited by 32 publications

References 26 publications

Cell sources forin vitrohuman liver cell culture models

Cell sources forin vitrohuman liver cell culture models

Pluripotent stem cells to hepatocytes, the journey so far

The Human Protein Atlas – an important resource for basic and clinical research

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