Evidence map›Paper›PMID 31310161›Full record

ArticleCirculation research2019

Physiological Biomimetic Culture System for Pig and Human Heart Slices.

Qinghui Ou, Zoë Jacobson, Riham R E Abouleisa, Xian-Liang Tang, Sajedah M Hindi, Ashok Kumar, Kathryn N Ivey, Guruprasad Giridharan, Ayman El-Baz, Kenneth Brittian and 10 more

Abstract read
In one paragraph

Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
–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

65 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Mechanisms and Therapeutic Potential of Human Cardiomyocyte Proliferation.Journal of cardiovascular development and disease · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Generation and applications of cardiac spheroids.npj biomedical innovations · 2025
    Review
  12. Right ventricle remodelling: fromJournal of molecular and cellular cardiology plus · 2025
    Review
  13. Review
  14. Review
  15. Article
  16. Article
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  18. Article
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  20. Article

5 more citing papers are in PubMed but not listed here.

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

20 authors.

Qinghui OuFrom the Department of Medicine, Institute of Molecular Cardiology (Q.O., R.R.E.A., X.-L.T., K.B., S.P.J., R.B., T.M.A.M.), University of Louisville, KY.
Zoë JacobsonTenaya Therapeutics, South San Francisco, CA (Z.J., K.N.I.).
Riham R E AbouleisaFrom the Department of Medicine, Institute of Molecular Cardiology (Q.O., R.R.E.A., X.-L.T., K.B., S.P.J., R.B., T.M.A.M.), University of Louisville, KY.
Xian-Liang TangFrom the Department of Medicine, Institute of Molecular Cardiology (Q.O., R.R.E.A., X.-L.T., K.B., S.P.J., R.B., T.M.A.M.), University of Louisville, KY.
Sajedah M HindiDepartments of Anatomical Sciences and Neurobiology (S.M.H., A.K.), University of Louisville, KY.
Ashok KumarDepartments of Anatomical Sciences and Neurobiology (S.M.H., A.K.), University of Louisville, KY.
Kathryn N IveyTenaya Therapeutics, South San Francisco, CA (Z.J., K.N.I.).
Guruprasad GiridharanDepartment of Bioengineering (G.G., A.E.-B.), University of Louisville, KY.
Ayman El-BazDepartment of Bioengineering (G.G., A.E.-B.), University of Louisville, KY.
Kenneth BrittianFrom the Department of Medicine, Institute of Molecular Cardiology (Q.O., R.R.E.A., X.-L.T., K.B., S.P.J., R.B., T.M.A.M.), University of Louisville, KY.
Benjamin RoodEnvirome Institute, Diabetes and Obesity Center, Department of Medicine (B.R., B.G.H., S.P.J., T.M.A.M.), University of Louisville, KY.
Ying-Hsi LinDivision of Cardiology and Consortium for Fibrosis Research & Translation, Department of Medicine, University of Colorado, Aurora (Y.-H.L., T.A.M.).
Samuel A WatsonNational Heart & Lung Institute, Imperial College London, United Kingdom (S.A.W., F.P., C.M.T.).
Filippo PerbelliniNational Heart & Lung Institute, Imperial College London, United Kingdom (S.A.W., F.P., C.M.T.).
Timothy A McKinseyDivision of Cardiology and Consortium for Fibrosis Research & Translation, Department of Medicine, University of Colorado, Aurora (Y.-H.L., T.A.M.).
Bradford G HillEnvirome Institute, Diabetes and Obesity Center, Department of Medicine (B.R., B.G.H., S.P.J., T.M.A.M.), University of Louisville, KY.
Steven P JonesFrom the Department of Medicine, Institute of Molecular Cardiology (Q.O., R.R.E.A., X.-L.T., K.B., S.P.J., R.B., T.M.A.M.), University of Louisville, KY.
Cesare M TerraccianoNational Heart & Lung Institute, Imperial College London, United Kingdom (S.A.W., F.P., C.M.T.).
Roberto BolliFrom the Department of Medicine, Institute of Molecular Cardiology (Q.O., R.R.E.A., X.-L.T., K.B., S.P.J., R.B., T.M.A.M.), University of Louisville, KY.
Tamer M A MohamedFrom the Department of Medicine, Institute of Molecular Cardiology (Q.O., R.R.E.A., X.-L.T., K.B., S.P.J., R.B., T.M.A.M.), University of Louisville, KY.

Funding

WKU Lead Faculty AwardP20GM103436 · NIGMS · UNIVERSITY OF LOUISVILLE · PI ERIC C ROUCHKA · 2012 to 2026
$60.1M
Tumor Necrosis Factor Modulation of CPCsP01HL078825 · NHLBI · UNIVERSITY OF LOUISVILLE · PI BOLLI, ROBERTO · 2005 to 2021
$37.6M
Regulation of Chromatin Signaling in Heart Failure by the BRD4 Bromodomain Protein.R01HL127240 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MCKINSEY, TIMOTHY, SRIVASTAVA, DEEPAK · 2015 to 2022
$6.4M
TBDP30GM127607 · NIGMS · UNIVERSITY OF LOUISVILLE · PI BHATNAGAR, ARUNI · 2018 to 2022
$6.3M
TAK1/TRAF6 Signaling in Skeletal MuscleR01AR059810 · NIAMS · UNIVERSITY OF LOUISVILLE · PI KUMAR, ASHOK · 2011 to 2021
$4.0M
Regulation of Cardiac Signaling by Class I Histone DeacetylasesR01HL116848 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MCKINSEY, TIMOTHY · 2013 to 2021
$3.1M
University of Louisville Regional Clinical Center for the CCTRNUM1HL113530 · NHLBI · UNIVERSITY OF LOUISVILLE · PI BOLLI, ROBERTO · 2012 to 2018
$2.9M
Effects of Air Pollution on Stem Cell HealthR01ES028268 · NIEHS · UNIVERSITY OF LOUISVILLE · PI HABERZETTL, PETRA, HILL, BRADFORD GUY · 2018 to 2022
$2.2M
Regulation of Metabolic Genes in the HeartR01HL131647 · NHLBI · UNIVERSITY OF LOUISVILLE · PI JONES, STEVEN P · 2016 to 2019
$2.2M
Screening and Development of Small Molecule HDAC11 Inhibitors to Treat Obesity and Diabetes.R01DK119594 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LIN, HENING, MCKINSEY, TIMOTHY · 2019 to 2022
$2.1M
Metabolic optimization of cell therapyR01HL130174 · NHLBI · UNIVERSITY OF LOUISVILLE · PI HILL, BRADFORD GUY · 2016 to 2020
$1.9M
Metabolic regulation of cardiac stem cellsR56HL122580 · NHLBI · UNIVERSITY OF LOUISVILLE · PI HILL, BRADFORD GUY · 2015 to 2015
$381k
British Heart Foundation FS/15/35/31529NHLBI NIH HHS P01 HL078825NHLBI NIH HHS R01 HL116848NHLBI NIH HHS R01 HL127240NHLBI NIH HHS R01 HL130174NHLBI NIH HHS R01 HL131647NHLBI NIH HHS R56 HL122580NHLBI NIH HHS UM1 HL113530NIAMS NIH HHS R01 AR059810NIDDK NIH HHS R01 DK119594NIEHS NIH HHS R01 ES028268NIGMS NIH HHS P20 GM103436NIGMS NIH HHS P30 GM127607
6 · The paper itself

Abstract

rationalePreclinical testing of cardiotoxicity and efficacy of novel heart failure therapies faces a major limitation: the lack of an in situ culture system that emulates the complexity of human heart tissue and maintains viability and functionality for a prolonged time.

objectiveTo develop a reliable, easily reproducible, medium-throughput method to culture pig and human heart slices under physiological conditions for a prolonged period of time. METHODS AND

resultsHere, we describe a novel, medium-throughput biomimetic culture system that maintains viability and functionality of human and pig heart slices (300 µm thickness) for 6 days in culture. We optimized the medium and culture conditions with continuous electrical stimulation at 1.2 Hz and oxygenation of the medium. Functional viability of these slices over 6 days was confirmed by assessing their calcium homeostasis, twitch force generation, and response to β-adrenergic stimulation. Temporal transcriptome analysis using RNAseq at day 2, 6, and 10 in culture confirmed overall maintenance of normal gene expression for up to 6 days, while over 500 transcripts were differentially regulated after 10 days. Electron microscopy demonstrated intact mitochondria and Z-disc ultra-structures after 6 days in culture under our optimized conditions. This biomimetic culture system was successful in keeping human heart slices completely viable and functionally and structurally intact for 6 days in culture. We also used this system to demonstrate the effects of a novel gene therapy approach in human heart slices. Furthermore, this culture system enabled the assessment of contraction and relaxation kinetics on isolated single myofibrils from heart slices after culture.

conclusionsWe have developed and optimized a reliable medium-throughput culture system for pig and human heart slices as a platform for testing the efficacy of novel heart failure therapeutics and reliable testing of cardiotoxicity in a 3-dimensional heart model.

Indexed as

AdultAnimalsBiomimeticsFemaleHeartHeart VentriclesHumansMaleMetabolomicsMiddle AgedMyocardiumOrgan Culture TechniquesSwineTranscriptomeVentricular Functioncalciumcardiotoxicitygenetic therapyheart failuretherapeutics

Identifiers

PMID31310161
PMCPMC6715512

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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.