Evidence map›Paper›PMID 34226515›Full record

ArticleCell death & disease2021

Valproic acid stimulates myogenesis in pluripotent stem cell-derived mesodermal progenitors in a NOTCH-dependent manner.

Natacha Breuls, Nefele Giarratana, Laura Yedigaryan, Gabriel Miró Garrido, Paolo Carai, Stephane Heymans, Adrian Ranga, Christophe Deroose, Maurilio Sampaolesi

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 26% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Inhibition of the EP300/Notch Signaling Pathway Regulates Proliferation and Apoptosis in Oral Squamous Cell Carcinoma.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026
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  3. Article
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  6. Valproic Acid Improves Antisense-Mediated Exon-Skipping Efficacy inInternational journal of molecular sciences · 2025
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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

9 authors at 5 institutions in 3 countries.

Natacha Breuls *Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000, Leuven, Belgium.
Nefele Giarratana *Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000, Leuven, Belgium.
Laura YedigaryanLaboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000, Leuven, Belgium.ORCID 0000-0002-1701-9109
Gabriel Miró GarridoLaboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000, Leuven, Belgium.
Paolo CaraiCARIM School for Cardiovascular Diseases, Department of Cardiology, Maastricht University, 6229 ER Maastricht, the Netherlands; Department of Cardiovascular Sciences, KU Leuven, 3000, Leuven, Belgium.
Stephane HeymansCARIM School for Cardiovascular Diseases, Department of Cardiology, Maastricht University, 6229 ER Maastricht, the Netherlands; Department of Cardiovascular Sciences, KU Leuven, 3000, Leuven, Belgium.
Adrian RangaLaboratory of Bioengineering and Morphogenesis, Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Leuven, Belgium.
Christophe DerooseDepartment of Nuclear Medicine, University Hospital KU Leuven, Leuven, Belgium.
Maurilio SampaolesiLaboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000, Leuven, Belgium. maurilio.sampaolesi@kuleuven.be.ORCID 0000-0002-2422-3757
Rega Institute for Medical Research · BEKU Leuven · BEMaastricht University · NLUniversity of Milan · ITUniversity of Pavia · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Muscular dystrophies are debilitating neuromuscular disorders for which no cure exists. As this disorder affects both cardiac and skeletal muscle, patients would benefit from a cellular therapy that can simultaneously regenerate both tissues. The current protocol to derive bipotent mesodermal progenitors which can differentiate into cardiac and skeletal muscle relies on the spontaneous formation of embryoid bodies, thereby hampering further clinical translation. Additionally, as skeletal muscle is the largest organ in the human body, a high myogenic potential is necessary for successful regeneration. Here, we have optimized a protocol to generate chemically defined human induced pluripotent stem cell-derived mesodermal progenitors (cdMiPs). We demonstrate that these cells contribute to myotube formation and differentiate into cardiomyocytes, both in vitro and in vivo. Furthermore, the addition of valproic acid, a clinically approved small molecule, increases the potential of the cdMiPs to contribute to myotube formation that can be prevented by NOTCH signaling inhibitors. Moreover, valproic acid pre-treated cdMiPs injected in dystrophic muscles increase physical strength and ameliorate the functional performances of transplanted mice. Taken together, these results constitute a novel approach to generate mesodermal progenitors with enhanced myogenic potential using clinically approved reagents.

Indexed as

AnimalsCell DifferentiationCell LineageCells, CulturedCoculture TechniquesDisease Models, AnimalFemaleHumansInduced Pluripotent Stem CellsMaleMesodermMiceMice, KnockoutMuscle ContractionMuscle DevelopmentMuscle Fibers, SkeletalReceptors, NotchValproic Acid

Identifiers

PMID34226515
PMCPMC8257578
OpenAlexW3182360373

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.