Evidence map›Paper›PMID 25982839›Full record

ArticleJournal of molecular and cellular cardiology2015

Comparable calcium handling of human iPSC-derived cardiomyocytes generated by multiple laboratories.

Hyun Seok Hwang, Dmytro O Kryshtal, T K Feaster, Verónica Sánchez-Freire, Jianhua Zhang, Timothy J Kamp, Charles C Hong, Joseph C Wu, Björn C Knollmann

Open access · hybridAbstract readComparative Study
In one paragraph

Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed
8.3field-weighted citation impact, top 2% 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

115 citing papers in PubMed, 166 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Fluorescence-lifetime optical electrophysiology in contracting cardiomyocytes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Review
  7. Review
  8. Sometimes extracellular recordings fail for good reasons.NPJ systems biology and applications · 2026
    Article
  9. mBio · 2026
    Article
  10. Article
  11. Review
  12. Large-scale synthetic data enable digital twins of human excitable cells.bioRxiv : the preprint server for biology · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Injectable biodegradable microcarriers for iPSC expansion and cardiomyocyte differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Hyun Seok HwangDivision of Clinical Pharmacology, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, Nashville, TN, USA.
Dmytro O KryshtalDivision of Clinical Pharmacology, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, Nashville, TN, USA.
T K FeasterDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Verónica Sánchez-FreireStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Jianhua ZhangDepartment of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.
Timothy J KampDepartment of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.
Charles C HongDivision of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN USA; Research Medicine, Veterans Affairs TVHS, Nasvhille, TN USA.
Joseph C WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Björn C KnollmannDivision of Clinical Pharmacology, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address: bjorn.knollmann@vanderbilt.edu.
Vanderbilt University · USStanford University · USUniversity of Wisconsin–Madison · USVeterans Health Administration · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI OWEN P MCGUINNESS · 2012 to 2026
$29.3M
TRANSGENIC MOUSE/ ES CELL SHARES RESOURCESP60DK020593 · NIDDK · VANDERBILT UNIVERSITY · PI MCGUINNESS, OWEN P · 1986 to 2011
$28.1M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kevin L Schey · 1989 to 2026
$19.6M
Vanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9M
Understanding and preventing HLA-associated drug reactionsP50GM115305 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DENNY, JOSHUA C. · 2015 to 2019
$13.0M
Midwest Progenitor Cell ConsortiumU01HL099773 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI THOMSON, JAMES ALEXANDER · 2009 to 2015
$7.8M
Vanderbilt Mouse Metabolic Phenotyping CenterU2CDK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2016 to 2021
$6.3M
Gene-Neurotoxicant Interactions in Huntington DiseaseR01ES016931 · NIEHS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BOWMAN, AARON B · 2008 to 2018
$4.5M
BLRD VA I01 BX000771NCATS NIH HHS UL1 TR000445NCI NIH HHS CA68485NCRR NIH HHS UL1 RR024975NEI NIH HHS EY08126NHLBI NIH HHS HL104040NHLBI NIH HHS HL108173NHLBI NIH HHS HL71670NHLBI NIH HHS HL88635NHLBI NIH HHS R01 HL071670NHLBI NIH HHS R01 HL088635NHLBI NIH HHS R01 HL104040NHLBI NIH HHS R01 HL108173NHLBI NIH HHS U01HL099773NIDDK NIH HHS DK20593NIDDK NIH HHS DK58404NIDDK NIH HHS DK59637NIDDK NIH HHS P30 DK020593NIEHS NIH HHS R01 ES016931NIGMS NIH HHS P50 GM115305NINDS NIH HHS R01 NS078289
6 · The paper itself

Abstract

Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are being increasingly used to model human heart diseases. hiPSC-CMs generated by earlier aggregation-based methods (i.e., embryoid body) often lack functional sarcoplasmic reticulum (SR) Ca stores characteristic of mature mammalian CMs. Newer monolayer-based cardiac differentiation methods (i.e., Matrigel sandwich or small molecule-based differentiation) produce hiPSC-CMs of high purity and yield, but their Ca handling has not been comprehensively investigated. Here, we studied Ca handling and cytosolic Ca buffering properties of hiPSC-CMs generated independently from multiple hiPSC lines at Stanford University, Vanderbilt University and University of Wisconsin-Madison. hiPSC-CMs were cryopreserved at each university. Frozen aliquots were shipped, recovered from cryopreservation, plated at low density and compared 3-5days after plating with acutely-isolated adult rabbit and mouse ventricular CMs. Although hiPSC-CM cell volume was significantly smaller, cell capacitance to cell volume ratio and cytoplasmic Ca buffering were not different from rabbit-CMs. hiPSC-CMs from all three laboratories exhibited robust L-type Ca currents, twitch Ca transients and caffeine-releasable SR Ca stores comparable to adult CMs. Ca transport by sarcoendoplasmic reticulum Ca ATPase (SERCA) and Na/Ca exchanger (NCX) was similar in all hiPSC-CM lines, but slower compared to rabbit-CMs. However, the relative contribution of SERCA and NCX to Ca transport of hiPSC-CMs was comparable to rabbit-CMs. Ca handling maturity of hiPSC-CMs increased from 15 to 21days post-induction. We conclude that hiPSC-CMs generated independently from multiple iPSC lines using monolayer-based methods can be reproducibly recovered from cryopreservation and exhibit comparable and functional SR Ca handling.

Indexed as

AnimalsCalciumCalcium SignalingCell DifferentiationCells, CulturedHumansInduced Pluripotent Stem CellsMiceMyocardial ContractionMyocytes, CardiacRabbitsSarcoplasmic ReticulumCalcium

Identifiers

PMID25982839
PMCPMC4530041
OpenAlexW1730627877

What OpenQuestion holds

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Registered trials

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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.