Evidence map›Paper›PMID 38229180›Full record

ArticleStem cell research & therapy2024

Vitamin C facilitates direct cardiac reprogramming by inhibiting reactive oxygen species.

Juntao Fang, Qiangbing Yang, Renée G C Maas, Michele Buono, Bram Meijlink, Dyonne Lotgerink Bruinenberg, Ernest Diez Benavente, Michal Mokry, Alain van Mil, Li Qian and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.3field-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, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Advances in fibroblast-based cardiac reprogramming in the treatment of heart disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  7. Article
  8. Enhanced fatty acid oxidation via SCD1 downregulation fuels cardiac reprogramming.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  9. Cell reprogramming: methods, mechanisms and applications.Cell regeneration (London, England) · 2025
    Review
  10. Review
  11. Review
  12. Article
  13. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Juntao FangExperimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Qiangbing Yang *Experimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Renée G C Maas *Experimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Michele BuonoExperimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Bram MeijlinkExperimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Dyonne Lotgerink BruinenbergExperimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Ernest Diez BenaventeExperimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Michal MokryExperimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Alain van MilExperimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Li QianMcAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA.
Marie-José GoumansDepartment of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.
Raymond SchiffelersCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Zhiyong LeiExperimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. Z.Lei-3@umcutrecht.nl.ORCID http://orcid.org/0000-0002-7194-7862
Joost P G SluijterExperimental Cardiology laboratory, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. J.Sluijter@umcutrecht.nl.
University Medical Center Utrecht · NLUtrecht University · NLLeiden University Medical Center · NLUniversity of North Carolina at Chapel Hill · US

Funding

European Research Council No. 725229
6 · The paper itself

Abstract

backgroundAfter myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to myocardial dysfunction. Direct reprogramming of fibroblasts into cardiomyocytes via the forced overexpression of cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) offers a promising strategy for cardiac repair. The limited reprogramming efficiency of this approach, however, remains a significant challenge.

methodsWe screened seven factors capable of improving direct cardiac reprogramming of both mice and human fibroblasts by evaluating small molecules known to be involved in cardiomyocyte differentiation or promoting human-induced pluripotent stem cell reprogramming.

resultsWe found that vitamin C (VitC) significantly increased cardiac reprogramming efficiency when added to GMT-overexpressing fibroblasts from human and mice in 2D and 3D model. We observed a significant increase in reactive oxygen species (ROS) generation in human and mice fibroblasts upon Doxy induction, and ROS generation was subsequently reduced upon VitC treatment, associated with increased reprogramming efficiency. However, upon treatment with dehydroascorbic acid, a structural analog of VitC but lacking antioxidant properties, no difference in reprogramming efficiency was observed, suggesting that the effect of VitC in enhancing cardiac reprogramming is partly dependent of its antioxidant properties.

conclusionsOur findings demonstrate that VitC supplementation significantly enhances the efficiency of cardiac reprogramming, partially by suppressing ROS production in the presence of GMT.

Indexed as

AntioxidantsAscorbic AcidAnimalsCellular ReprogrammingFibroblastsHumansMEF2 Transcription FactorsMiceMyocytes, CardiacReactive Oxygen SpeciesT-Box Domain ProteinsVitaminsAntioxidantsAscorbic AcidMEF2 Transcription FactorsReactive Oxygen SpeciesT-Box Domain ProteinsVitaminsCardiac regenerationCardiac reprogrammingROSVitamin C

Identifiers

PMID38229180
PMCPMC10792814
OpenAlexW4390928551

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.