Evidence map›Paper›PMID 41349535›Full record

ArticleStem cell reports2026

Cross-modal integration of metabolomics and cardiac functionality captures dynamic metabotoxic effects of doxorubicin in engineered heart tissues.

Federica Conte, Doroteya K Staykova, Carla Cofiño-Fabres, Danique Snippert, Arno van Rooij, Dirk J Lefeber, Robert Passier

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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.

Federica ConteDepartment of Human Genetics, Translational Metabolic Laboratory (TML), Radboud University Medical Center, 6525GA Nijmegen, the Netherlands; Applied Stem Cell Technologies Group, Department of Bioengineering Technologies, TechMed Centre, University of Twente, 7522NB Enschede, the Netherlands; Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
Doroteya K StaykovaDepartment of Human Genetics, Translational Metabolic Laboratory (TML), Radboud University Medical Center, 6525GA Nijmegen, the Netherlands; United for Metabolic Diseases, National Infrastructure for Metabolic Disease Research, the Netherlands; Multicore Dynamics Ltd, New Milton, UK.
Carla Cofiño-FabresApplied Stem Cell Technologies Group, Department of Bioengineering Technologies, TechMed Centre, University of Twente, 7522NB Enschede, the Netherlands.
Danique SnippertApplied Stem Cell Technologies Group, Department of Bioengineering Technologies, TechMed Centre, University of Twente, 7522NB Enschede, the Netherlands.
Arno van RooijDepartment of Human Genetics, Translational Metabolic Laboratory (TML), Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
Dirk J LefeberDepartment of Human Genetics, Translational Metabolic Laboratory (TML), Radboud University Medical Center, 6525GA Nijmegen, the Netherlands; Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands; United for Metabolic Diseases, National Infrastructure for Metabolic Disease Research, the Netherlands. Electronic address: Dirk.Lefeber@radboudumc.nl.
Robert PassierApplied Stem Cell Technologies Group, Department of Bioengineering Technologies, TechMed Centre, University of Twente, 7522NB Enschede, the Netherlands; Department of Anatomy and Embryology, Leiden University Medical Centre, 2311EZ Leiden, the Netherlands. Electronic address: robert.passier@utwente.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Functional stem cell-derived heart models offer new avenues for preclinical, animal-free physiological assessment of drug cardiotoxicity. Yet, comprehensive molecular profiling in these models remains limited, leaving key metabolic drivers of cardiotoxicity unexplored. Here, we leveraged an innovative platform and a topology-guided integration framework to unveil the complex dose- and time-dependent metabolic rewiring of the central carbon metabolism caused by doxorubicin-induced cardiotoxicity (DiC) in human heart tissue. Through cross-modal integration of cardiac functionality and metabolomics in 3D engineered heart tissues, we identified 20 metabolites linked to cardiac contraction and differentially affected by doxorubicin exposure. Nine of them, including carnitine esters and uridine 5'-diphosphate (UDP)-glucuronic acid, were never before implicated in DiC and may represent promising candidates for DiC metabolic rescue. By yielding high-resolution insights into complex biological mechanisms, our platform and mathematical framework enable metabolic and functional assessment of cardiotoxicity in engineered heart models, paving the way for innovative advances in preclinical drug development.

Indexed as

DoxorubicinHeartMetabolomeMetabolomicsMyocardiumTissue EngineeringCardiotoxicityHumansMyocytes, CardiacDoxorubicin3D engineered heart tissuecardiotoxicitycross-modal integrationdrug screeningforce of contractionheart-on-chipmetabolomicsmulti-omics integrationtopological data analysistopological node enrichment

Identifiers

PMID41349535
PMCPMC12925965

What Socratic 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 Socratic graph.