Evidence map›Paper›PMID 30874583›Full record

ArticleScientific reports2019

In vitro metabolic activation of vitamin D3 by using a multi-compartment microfluidic liver-kidney organ on chip platform.

Jannick Theobald, Mohamed A Abu El Maaty, Nico Kusterer, Bernhard Wetterauer, Michael Wink, Xinlai Cheng, Stefan Wölfl

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
2.7field-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

27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.

  1. Pooled it
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  10. Tissue chips as headway model and incitement technology.Synthetic and systems biotechnology · 2025
    Review
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  17. Article
  18. Organs-on-chip technology: a tool to tackle genetic kidney diseases.Pediatric nephrology (Berlin, Germany) · 2022
    Review
  19. Article
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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

7 authors at 1 institution in 1 country.

Jannick TheobaldInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany.
Mohamed A Abu El MaatyInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany.
Nico KustererInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany.
Bernhard WetterauerInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany.
Michael WinkInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany.
Xinlai ChengInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany.ORCID 0000-0001-6441-3742
Stefan WölflInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany. wolfl@uni-hd.de.
Heidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Organ-on-chip platforms provide models that allow the representation of human physiological processes in cell-based miniaturized systems. Potential pre-clinical applications include drug testing and toxicity studies. Here we describe the use of a multi-compartment micro-fluidic chip to recapitulate hepatic vitamin D metabolism (vitamin D to 25-hydroxyvitamin D) and renal bio-activation (25-hydroxyvitamin D to 1,25-dihydroxyvitamin D) in humans. In contrast to cultivation in conventional tissue culture settings, on-chip cultivation of HepG2 and RPTEC cells in interconnected chambers, used to mimic the liver and kidneys, respectively, resulted in the enhanced expression of vitamin D metabolizing enzymes (CYP2R1, CYP27B1 and CYP24A1). Pump-driven flow of vitamin D3-containing medium through the microfluidic chip produced eluate containing vitamin D3 metabolites. LC-MSMS showed a strong accumulation of 25-hydroxyvitamin D. The chip eluate induced the expression of differentiation markers in HL-60 (acute myeloid leukemia) cells, assessed by qPCR and FACS analysis, in a manner similar to treatment with reference standards indicating the presence of fully activated 1,25 dihydroxyvitamin D, although the latter was not detected in the eluate by LC-MSMS. Interestingly, 25-hydroxyvitamin D by itself led to weak activation of HL-60 cells suggesting that 25-hydroxyvitamin D is also an active metabolite. Our experiments demonstrate that complex metabolic interactions can be reconstructed outside the human body using dedicated organ-on-chip platforms. We therefore propose that such systems may be used to mimic the in vivo metabolism of various micronutrients and xenobiotics.

Indexed as

25-Hydroxyvitamin D3 1-alpha-HydroxylaseActivation, MetabolicAnimalsCell LineCholecalciferolCytochrome P-450 Enzyme SystemHep G2 CellsHL-60 CellsHumansKidneyLab-On-A-Chip DevicesLiverMicrochip Analytical ProceduresMicrofluidic Analytical TechniquesMicrofluidicsVitamin D25-hydroxyvitamin D25-Hydroxyvitamin D3 1-alpha-HydroxylaseCholecalciferolCytochrome P-450 Enzyme SystemVitamin DVitamins

Identifiers

PMID30874583
PMCPMC6420623
OpenAlexW2922123973

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.