Evidence map›Paper›PMID 35159346›Full record

ArticleCells2022

Evidence of Adult Features and Functions of Hepatocytes Differentiated from Human Induced Pluripotent Stem Cells and Self-Organized as Organoids.

Antonietta Messina, Eléanor Luce, Nassima Benzoubir, Mattia Pasqua, Ulysse Pereira, Lydie Humbert, Thibaut Eguether, Dominique Rainteau, Jean-Charles Duclos-Vallée, Cécile Legallais and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
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  9. Liver organoid culture methods.Cell & bioscience · 2023
    Review
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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

11 authors at 2 institutions in 1 country.

Antonietta MessinaUMR_S 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, France.ORCID 0000-0002-5610-973X
Eléanor LuceUMR_S 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, France.ORCID 0000-0002-8938-8405
Nassima BenzoubirUMR_S 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, France.ORCID 0000-0001-7502-7441
Mattia PasquaCentre Hépatobiliaire, Fédération Hospitalo-Universitaire (FHU) Hépatinov, AP-HP, Hôpital Paul Brousse, F-94800 Villejuif, France.ORCID 0000-0002-8312-6041
Ulysse PereiraCentre Hépatobiliaire, Fédération Hospitalo-Universitaire (FHU) Hépatinov, AP-HP, Hôpital Paul Brousse, F-94800 Villejuif, France.ORCID 0000-0001-5677-6906
Lydie HumbertCentre de Recherche Saint-Antoine, Sorbonne Université, INSERM, CRSA, AP-HP, Hôpital Saint Antoine, Metomics, 75012 Paris, France.
Thibaut EguetherCentre de Recherche Saint-Antoine, Sorbonne Université, INSERM, CRSA, AP-HP, Hôpital Saint Antoine, Metomics, 75012 Paris, France.ORCID 0000-0003-1891-9253
Dominique RainteauCentre de Recherche Saint-Antoine, Sorbonne Université, INSERM, CRSA, AP-HP, Hôpital Saint Antoine, Metomics, 75012 Paris, France.
Jean-Charles Duclos-ValléeUMR_S 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, France.
Cécile LegallaisCentre Hépatobiliaire, Fédération Hospitalo-Universitaire (FHU) Hépatinov, AP-HP, Hôpital Paul Brousse, F-94800 Villejuif, France.ORCID 0000-0002-8061-906X
Anne Dubart-KupperschmittUMR_S 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, France.ORCID 0000-0002-9326-4413
Inserm · FRUniversité de Technologie de Compiègne · FR

Funding

Agence Nationale de la Recherche ANR-16-RHUS-0005
6 · The paper itself

Abstract

backgroundHuman-induced pluripotent stem cell-derived hepatocytes (iHeps) have been shown to have considerable potential in liver diseases, toxicity, and pharmacological studies. However, there is a growing need to obtain iHeps that are truly similar to primary adult hepatocytes in terms of morphological features and functions. We generated such human iHeps, self-assembled as organoids (iHep-Orgs).

methodsiPSC-derived hepatoblasts were self-assembled into spheroids and differentiated into mature hepatocytes modulating final step of differentiation.

resultsIn about four weeks of culture, the albumin secretion levels and the complete disappearance of α-fetoprotein from iHep-Orgs suggested the acquisition of a greater degree of maturation than those previously reported. The expression of apical transporters and bile acid secretion evidenced the acquisition of complex hepatocyte polarity as well as the development of a functional and well-defined bile canalicular network confirmed by computational analysis. Activities recorded for CYP450, UGT1A1, and alcohol dehydrogenase, response to hormonal stimulation, and glucose metabolism were also remarkable. Finally, iHep-Orgs displayed a considerable ability to detoxify pathological concentrations of lactate and ammonia.

conclusionsWith features similar to those of primary adult hepatocytes, the iHep-Orgs thus produced could be considered as a valuable tool for the development and optimization of preclinical and clinical applications.

Indexed as

Induced Pluripotent Stem CellsLiver DiseasesAdultCell DifferentiationHepatocytesHumansOrganoidsbile acidsbile canaliculi networkdetoxificationhepatic mature functionshiPSC-derived hepatocyteshiPSCsHLCsliver organoidsmetabolismself-assembling

Identifiers

PMID35159346
PMCPMC8834365
OpenAlexW4210543720

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.