Evidence map›Paper›PMID 40614731›Full record

ArticleStem cell reports2025

Developmental cues from epicardial cells simultaneously promote cardiomyocyte proliferation and electrochemical maturation.

Sophie E Givens, Abygail A Andebrhan, Ruchen Wang, Xiangzhen Kong, Taylor M Rothermel, Sanaz Hosseini, An Xie, Mohammad Shameem, Andrea A Torniainen, Somayeh Ebrahimi-Barough and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Early Cytoskeletal Remodeling Drives Hypertrophic Cardiomyopathy Pathogenesis inJournal of cardiovascular development and disease · 2025
    Article
  3. Review
  4. 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

19 authors.

Sophie E GivensBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Abygail A AndebrhanBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Ruchen WangLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Xiangzhen KongBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Taylor M RothermelBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Sanaz HosseiniElectrical Engineering, University of Minnesota, Minneapolis, MN, USA.
An XieLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Mohammad ShameemBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA; Department of Rehabilitation Medicine, University of Minnesota, Minneapolis, MN, USA.
Andrea A TorniainenLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Somayeh Ebrahimi-BaroughBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Samuel F BolandBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Maya JohnsonBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Natalia Calixto MancipeMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA.
Bhairab N SinghBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA; Department of Rehabilitation Medicine, University of Minnesota, Minneapolis, MN, USA.
Samuel DudleyLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Patrick W AlfordBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Elena G TolkachevaBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA; Lillehei Heart Institute (LHI), Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Electrical Engineering, University of Minnesota, Minneapolis, MN, USA; Institute of Engineering in Medicine, University of Minnesota, Minneapolis, MN, USA.
Jop H van BerloLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.
Brenda M OgleBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Institute of Engineering in Medicine, University of Minnesota, Minneapolis, MN, USA. Electronic address: ogle@umn.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Accumulating evidence indicates that maturation limits cardiomyocyte proliferation. We expand on that theory by co-culturing human induced pluripotent stem cell (hiPSC)-cardiomyocytes (CM) with epicardial cells (EPCs) and epicardial-derived cells in both 2D co-cultures and 3D engineered heart tissues (EHTs). In 2D co-cultures, the percentage of proliferating CM increased in parallel with stark electrophysiologic improvements. Single-cell transcriptomics revealed a significant shift in the bulk CM population of the epicardial-CM co-cultures as characterized by more fetal-like myofilament isoforms but with enhanced pathways associated with electrochemical maturation. The 3D-EHTs containing EPCs showed more limited proliferation but a similar improvement in CM electrophysiologic function. Next, epicardial-derived fibroblasts (EPD-FBs) were added to the EHTs containing EPCs, and we observed significant myofilament maturation and increased force generation. Our results suggest that some aspects of CM maturation (i.e., electrochemical) can occur when proliferation rates are relatively high, and that sarcomere-associated mechanical maturation occurs at later developmental stages when proliferation has largely ceased.

Indexed as

Cell DifferentiationMyocytes, CardiacPericardiumCell ProliferationCells, CulturedCoculture TechniquesFibroblastsHumansInduced Pluripotent Stem CellsTissue Engineeringcalcium handlingcardiac maturationcardiomyocyte proliferationengineered heart tissuesepicardial cellshuman induced pluripotent stem cells

Identifiers

PMID40614731
PMCPMC12365841

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.