Evidence map›Paper›PMID 32459996›Full record

ArticleCell stem cell2020

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease.

Elisa Giacomelli, Viviana Meraviglia, Giulia Campostrini, Amy Cochrane, Xu Cao, Ruben W J van Helden, Ana Krotenberg Garcia, Maria Mircea, Sarantos Kostidis, Richard P Davis and 19 more

Open access · hybridAbstract read
In one paragraph

Article in Cell stem cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 387 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
387citing papers in PubMed, 1 pooled it
70.1field-weighted citation impact, top 1% 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

387 citing papers in PubMed, 1 synthesis or guideline pooled it, 585 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 6 institutions in 3 countries.

Elisa GiacomelliDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Viviana MeravigliaDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Giulia CampostriniDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Amy CochraneDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Xu CaoDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Ruben W J van HeldenDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Ana Krotenberg GarciaDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Maria MirceaLeiden Institute of Physics, Leiden University, 2333 Leiden, the Netherlands.
Sarantos KostidisCenter for Proteomics and Metabolomics, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Richard P DavisDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Berend J van MeerDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Carolina R JostDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Abraham J KosterDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Hailiang MeiSequencing Analysis Support Core, Leiden University Medical Center, 2333 Leiden, the Netherlands.
David G MíguezCentro de Biologia Molecular Severo Ochoa, Departamento de Física de la Materia Condensada, Instituto Nicolas Cabrera and Condensed Matter Physics Center (IFIMAC), Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Aat A MulderDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Mario Ledesma-TerrónCentro de Biologia Molecular Severo Ochoa, Departamento de Física de la Materia Condensada, Instituto Nicolas Cabrera and Condensed Matter Physics Center (IFIMAC), Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Giulio PompilioVascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy.
Luca SalaDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Daniela C F SalvatoriCentral Laboratory Animal Facility, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Roderick C SliekerDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 Leiden, the Netherlands; Department of Epidemiology and Biostatistics, Amsterdam Public Health Institute, VU University Medical Center, 1007 Amsterdam, the Netherlands.
Elena SommarivaVascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy.
Antoine A F de VriesDepartment of Cardiology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Martin GieraCenter for Proteomics and Metabolomics, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Stefan SemrauLeiden Institute of Physics, Leiden University, 2333 Leiden, the Netherlands.
Leon G J TertoolenDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands.
Valeria V OrlovaDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands. Electronic address: v.orlova@lumc.nl.
Milena BellinDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands; Department of Biology, University of Padua, 35121 Padua, Italy; Veneto Institute of Molecular Medicine, 35129 Padua, Italy. Electronic address: m.bellin@lumc.nl.
Christine L MummeryDepartment of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands; Department of Applied Stem Cell Technologies, University of Twente, 7500 Enschede, the Netherlands. Electronic address: c.l.mummery@lumc.nl.
Leiden University Medical Center · NLCentro de Biología Molecular Severo Ochoa · ESLeiden University · NLCentro Cardiologico Monzino · ITUniversity of Milan · ITUniversity of Padua · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and cardiac endothelial cells also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs in MTs with CFs showed improved sarcomeric structures with T-tubules, enhanced contractility, and mitochondrial respiration and were electrophysiologically more mature than MTs without CFs. Interactions mediating maturation included coupling between hiPSC-CMs and CFs through connexin 43 (CX43) gap junctions and increased intracellular cyclic AMP (cAMP). Scaled production of thousands of hiPSC-MTs was highly reproducible across lines and differentiated cell batches. MTs containing healthy-control hiPSC-CMs but hiPSC-CFs from patients with arrhythmogenic cardiomyopathy strikingly recapitulated features of the disease. Our MT model is thus a simple and versatile platform for modeling multicellular cardiac diseases that will facilitate industry and academic engagement in high-throughput molecular screening.

Indexed as

Heart DiseasesInduced Pluripotent Stem CellsCell DifferentiationEndothelial CellsHumansMyocytes, CardiacStromal Cellsarrhythmogenic cardiomyopathycAMPcardiac disease modelcardiac microtissuecardiomyocyte maturationcell-cell interactioncyclic AMPgap junctionhuman-induced-pluripotent-stem-cell-derived cardiac fibroblastshuman-induced-pluripotent-stem-cell-derived cardiomyocytes

Identifiers

PMID32459996
PMCPMC7284308
OpenAlexW3029730275

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.