Evidence map›Paper›PMID 31940797›Full record

ArticleInternational journal of molecular sciences2020

Characterization of Human Induced Pluripotent Stem Cell-Derived Hepatocytes with Mature Features and Potential for Modeling Metabolic Diseases.

Gustav Holmgren, Benjamin Ulfenborg, Annika Asplund, Karin Toet, Christian X Andersson, Ann Hammarstedt, Roeland Hanemaaijer, Barbara Küppers-Munther, Jane Synnergren

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 23 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Gustav HolmgrenSystems biology research center, School of Bioscience, University of Skövde, 54128 Skövde, Sweden.ORCID 0000-0002-0402-1437
Benjamin UlfenborgSystems biology research center, School of Bioscience, University of Skövde, 54128 Skövde, Sweden.ORCID 0000-0001-9242-4852
Annika AsplundR&D, Hepatocyte Product Development, Takara Bio Europe AB, 41346 Gothenburg, Sweden.
Karin ToetDepartment of Metabolic Health Research, TNO, 2333 Leiden, The Netherlands.
Christian X AnderssonR&D, Hepatocyte Product Development, Takara Bio Europe AB, 41346 Gothenburg, Sweden.
Ann HammarstedtThe Lundberg Laboratory for Diabetes Research, Departments of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden.
Roeland HanemaaijerDepartment of Metabolic Health Research, TNO, 2333 Leiden, The Netherlands.
Barbara Küppers-MuntherR&D, Hepatocyte Product Development, Takara Bio Europe AB, 41346 Gothenburg, Sweden.ORCID 0000-0003-4217-9355
Jane SynnergrenSystems biology research center, School of Bioscience, University of Skövde, 54128 Skövde, Sweden.
Takara (Sweden) · SEUniversity of Skövde · SENetherlands Organisation for Applied Scientific Research · NLUniversity of Gothenburg · SE

Funding

Knowledge Foundation 2014/0301, 2016/0293 and 2017/0302
6 · The paper itself

Abstract

There is a strong anticipated future for human induced pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far, their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The transcriptomics analysis revealed that 86% of the genes were expressed at similar levels in hiPS-HEP as in human primary hepatocytes (hphep). Adult characteristics of the hiPS-HEP were confirmed by the presence of important hepatocyte features, e.g., Albumin secretion and expression of major drug metabolizing genes. Normal energy metabolism is crucial for modeling metabolic diseases, and both transcriptomics data and functional assays showed that hiPS-HEP were similar to hphep regarding uptake of glucose, low-density lipoproteins (LDL), and fatty acids. Importantly, the inflammatory state of the hiPS-HEP was low under standard conditions, but in response to lipid accumulation and ER stress the inflammation marker tumor necrosis factor α (TNFα) was upregulated. Furthermore, hiPS-HEP could be co-cultured with primary hepatic stellate cells both in 2D and in 3D spheroids, paving the way for using these co-cultures for modeling non-alcoholic steatohepatitis (NASH). Taken together, hiPS-HEP have the potential to serve as an in vitro model for metabolic diseases. Furthermore, differently expressed genes identified in this study can serve as targets for future improvements of the hiPS-HEP.

Indexed as

TranscriptomeAgedCell DifferentiationCell LineCells, CulturedEndoplasmic Reticulum StressEnergy MetabolismFatty AcidsFemaleGlucoseHepatocytesHumansInduced Pluripotent Stem CellsLipoproteins, LDLMaleMetabolic DiseasesFatty AcidsGlucoseLipoproteins, LDLcharacterizationhuman induced pluripotent stem cellshuman stem cell-derived hepatocytesin vitromaturationmetabolic diseasestranscriptomics

Identifiers

PMID31940797
PMCPMC7014160
OpenAlexW2995115429

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.