Evidence map›Paper›PMID 29039463›Full record

ArticleInternational journal of molecular medicine2017

Hepatic differentiation of human iPSCs in different 3D models: A comparative study.

Florian Meier, Nora Freyer, Joanna Brzeszczynska, Fanny Knöspel, Lyle Armstrong, Majlinda Lako, Selina Greuel, Georg Damm, Eva Ludwig-Schwellinger, Ulrich Deschl and 3 more

Abstract readComparative Study
In one paragraph

Article in International journal of molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
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

30 citing papers in PubMed.

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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

13 authors.

Florian MeierBoehringer Ingelheim Pharma GmbH and Co.KG, Nonclinical Drug Safety Germany, D-88397 Biberach an der Riss, Germany.
Nora FreyerBioreactor Group, Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, D-13353 Berlin, Germany.
Joanna BrzeszczynskaTissue Injury and Repair Group, Chancellor's Building, Edinburgh Medical School, University of Edinburgh, EH164SB Edinburgh, UK.
Fanny KnöspelBioreactor Group, Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, D-13353 Berlin, Germany.
Lyle ArmstrongInstitute of Genetic Medicine, University of Newcastle upon Tyne, NE13BZ Newcastle upon Tyne, UK.
Majlinda LakoInstitute of Genetic Medicine, University of Newcastle upon Tyne, NE13BZ Newcastle upon Tyne, UK.
Selina GreuelBioreactor Group, Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, D-13353 Berlin, Germany.
Georg DammDepartment of Hepatobiliary Surgery and Visceral Transplantation, University of Leipzig, D-04103 Leipzig, Germany.
Eva Ludwig-SchwellingerBoehringer Ingelheim Pharma GmbH and Co.KG, Drug Metabolism and Pharmacokinetics Germany, D-88397 Biberach an der Riss, Germany.
Ulrich DeschlBoehringer Ingelheim Pharma GmbH and Co.KG, Nonclinical Drug Safety Germany, D-88397 Biberach an der Riss, Germany.
James A RossTissue Injury and Repair Group, Chancellor's Building, Edinburgh Medical School, University of Edinburgh, EH164SB Edinburgh, UK.
Mario BeilmannBoehringer Ingelheim Pharma GmbH and Co.KG, Nonclinical Drug Safety Germany, D-88397 Biberach an der Riss, Germany.
Katrin ZeilingerBioreactor Group, Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, D-13353 Berlin, Germany.

Funding

Biotechnology and Biological Sciences Research Council BB/E012841/1Medical Research Council G0301182
6 · The paper itself

Abstract

Human induced pluripotent stem cells (hiPSCs) are a promising source from which to derive distinct somatic cell types for in vitro or clinical use. Existent protocols for hepatic differentiation of hiPSCs are primarily based on 2D cultivation of the cells. In the present study, the authors investigated the generation of hiPSC-derived hepatocyte-like cells using two different 3D culture systems: A 3D scaffold-free microspheroid culture system and a 3D hollow-fiber perfusion bioreactor. The differentiation outcome in these 3D systems was compared with that in conventional 2D cultures, using primary human hepatocytes as a control. The evaluation was made based on specific mRNA expression, protein secretion, antigen expression and metabolic activity. The expression of α-fetoprotein was lower, while cytochrome P450 1A2 or 3A4 activities were higher in the 3D culture systems as compared with the 2D differentiation system. Cells differentiated in the 3D bioreactor showed an increased expression of albumin and hepatocyte nuclear factor 4α, as well as secretion of α-1-antitrypsin as compared with the 2D differentiation system, suggesting a higher degree of maturation. In contrast, the 3D scaffold-free microspheroid culture provides an easy and robust method to generate spheroids of a defined size for screening applications, while the bioreactor culture model provides an instrument for complex investigations under physiological-like conditions. In conclusion, the present study introduces two 3D culture systems for stem cell derived hepatic differentiation each demonstrating advantages for individual applications as well as benefits in comparison with 2D cultures.

Indexed as

Cell Culture TechniquesModels, BiologicalBioreactorsCell DifferentiationCell LineEquipment DesignHepatocytesHumansInduced Pluripotent Stem CellsPerfusion

Identifiers

PMID29039463
PMCPMC5716452

What OpenQuestion holds

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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.