Evidence map›Paper›PMID 28646906›Full record

ArticleStem cell research & therapy2017

Modulation of oxidative phosphorylation and redox homeostasis in mitochondrial NDUFS4 deficiency via mesenchymal stem cells.

Marlen Melcher, Katharina Danhauser, Annette Seibt, Özer Degistirici, Fabian Baertling, Arun Kumar Kondadi, Andreas S Reichert, Werner J H Koopman, Peter H G M Willems, Richard J Rodenburg and 3 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

23 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
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  3. Mitochondrial complex I deficiency-associated diseases and models.Cellular and molecular life sciences : CMLS · 2026
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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 at 4 institutions in 2 countries.

Marlen MelcherDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
Katharina DanhauserDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
Annette SeibtDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
Özer DegistiriciDivision of Pediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University Medical Center, Düsseldorf, Germany.
Fabian BaertlingDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
Arun Kumar KondadiInstitute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Andreas S ReichertInstitute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Werner J H KoopmanDepartment of Biochemistry (286), Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen (Radboudumc), Nijmegen, The Netherlands.
Peter H G M WillemsDepartment of Biochemistry (286), Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen (Radboudumc), Nijmegen, The Netherlands.
Richard J RodenburgRadboud Center for Mitochondrial Medicine (RCMM), Department of Pediatrics, 774 Translational Metabolic Laboratory (TML), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Ertan MayatepekDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
Roland MeiselDivision of Pediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University Medical Center, Düsseldorf, Germany.
Felix DistelmaierDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany. Felix.Distelmaier@med.uni-duesseldorf.de.
Heinrich Heine University Düsseldorf · DEDüsseldorf University Hospital · DERadboud Institute for Molecular Life Sciences · NLRadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDisorders of the oxidative phosphorylation (OXPHOS) system represent a large group among the inborn errors of metabolism. The most frequently observed biochemical defect is isolated deficiency of mitochondrial complex I (CI). No effective treatment strategies for CI deficiency are so far available. The purpose of this study was to investigate whether and how mesenchymal stem cells (MSCs) are able to modulate metabolic function in fibroblast cell models of CI deficiency.

methodsWe used human and murine fibroblasts with a defect in the nuclear DNA encoded NDUFS4 subunit of CI. Fibroblasts were co-cultured with MSCs under different stress conditions and intercellular mitochondrial transfer was assessed by flow cytometry and fluorescence microscopy. Reactive oxygen species (ROS) levels were measured using MitoSOX-Red. Protein levels of CI were analysed by blue native polyacrylamide gel electrophoresis (BN-PAGE).

resultsDirect cellular interactions and mitochondrial transfer between MSCs and human as well as mouse fibroblast cell lines were demonstrated. Mitochondrial transfer was visible in 13.2% and 6% of fibroblasts (e.g. fibroblasts containing MSC mitochondria) for human and mouse cell lines, respectively. The transfer rate could be further stimulated via treatment of cells with TNF-α. MSCs effectively lowered cellular ROS production in NDUFS4-deficient fibroblast cell lines (either directly via co-culture or indirectly via incubation of cell lines with cell-free MSC supernatant). However, CI protein expression and activity were not rescued by MSC treatment.

conclusionThis study demonstrates the interplay between MSCs and fibroblast cell models of isolated CI deficiency including transfer of mitochondria as well as modulation of cellular ROS levels. Further exploration of these cellular interactions might help to develop MSC-based treatment strategies for human CI deficiency.

Indexed as

Electron Transport Complex INADH DehydrogenaseOxidative PhosphorylationAnimalsCoculture TechniquesFibroblastsHumansMesenchymal Stem CellsMiceMitochondriaElectron Transport Complex INADH DehydrogenaseNDUFS4 protein, humanNdufs4 protein, mouse

Identifiers

PMID28646906
PMCPMC5482938
OpenAlexW2643604317

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.