Evidence map›Paper›PMID 26159124›Full record

ArticleScientific reports2015

Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells.

Ilya Y Shadrin, Woohyun Yoon, Liqing Li, Neal Shepherd, Nenad Bursac

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.8field-weighted citation impact, top 7% 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, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. 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

5 authors at 1 institution in 1 country.

Ilya Y ShadrinDepartment of Biomedical Engineering, Duke University, Durham, NC.
Woohyun YoonDepartment of Biomedical Engineering, Duke University, Durham, NC.
Liqing LiDepartment of Biomedical Engineering, Duke University, Durham, NC.
Neal ShepherdDepartment of Biomedical Engineering, Duke University, Durham, NC.
Nenad BursacDepartment of Biomedical Engineering, Duke University, Durham, NC.
Duke University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007171 · NIGMS · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 1985 to 2021
$31.2M
Function and Integration of Stem Cell-derived Cardiac Tissue PatchR01HL104326 · NHLBI · DUKE UNIVERSITY · PI BURSAC, NENAD · 2010 to 2014
$1.8M
Mechanisms for Stem Cell Differentiation into Cardiac MyocytesR01HL091348 · NHLBI · DUKE UNIVERSITY · PI KIRBY, MARGARET LOEWY · 2009 to 2010
$1.3M
Functional 3D Cardiac Patches Derived from Human Induced Pluripotent Stem CellsF30HL122079 · NHLBI · DUKE UNIVERSITY · PI SHADRIN, ILYA Y. · 2014 to 2015
$65k
NHLBI NIH HHS F30 HL122079NHLBI NIH HHS HL091348NHLBI NIH HHS HL104326NHLBI NIH HHS HL122079NHLBI NIH HHS R01 HL091348NHLBI NIH HHS R01 HL104326NIGMS NIH HHS T32 GM007171NIGMS NIH HHS T32 GM 7171-38
6 · The paper itself

Abstract

Cardiac cell therapies involving bone marrow-derived human mesenchymal stem cells (hMSCs) have shown promising results, although their mechanisms of action are still poorly understood. Here, we investigated direct interactions between hMSCs and cardiomyocytes in vitro. Using a genetic Ca(2+) indicator gCaMP3 to efficiently label hMSCs in co-cultures with neonatal rat ventricular myocytes (NRVMs), we determined that 25-40% of hMSCs (from 4 independent donors) acquired periodic Ca(2+) transients and cardiac markers through spontaneous fusion with NRVMs. Sharp electrode and voltage-clamp recordings in fused cells showed action potential properties and Ca(2+) current amplitudes in between those of non-fused hMSCs and NRVMs. Time-lapse video-microscopy revealed the first direct evidence of active fusion between hMSCs and NRVMs within several hours of co-culture. Application of blebbistatin, nifedipine or verapamil caused complete and reversible inhibition of fusion, suggesting potential roles for actomyosin bridging and Ca(2+) channels in the fusion process. Immunostaining for Cx43, Ki67, and sarcomeric α-actinin showed that fused cells remain strongly coupled to surrounding NRVMs, but downregulate sarcomeric structures over time, acquiring a non-proliferative and non-contractile phenotype. Overall, these results describe the phenotype and mechanisms of hybrid cell formation via fusion of hMSCs and cardiomyocytes with potential implications for cardiac cell therapy.

Indexed as

Cell FusionActininAction PotentialsAnimalsCaffeineCalciumCalcium Channels, L-TypeCell MovementCells, CulturedCoculture TechniquesConnexin 43HumansIonsMesenchymal Stem CellsMicroscopy, VideoMyocytes, CardiacActininCaffeineCalciumCalcium Channels, L-TypeConnexin 43IonsMyosin Type IITroponin T

Identifiers

PMID26159124
PMCPMC4498233
OpenAlexW801920303

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.