Evidence map›Paper›PMID 23461462›Full record

ArticleStem cells and development2013

Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells.

Scott D Lundy, Wei-Zhong Zhu, Michael Regnier, Michael A Laflamme

Open access · greenAbstract read
In one paragraph

Article in Stem cells and development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 463 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
463citing papers in PubMed, 2 pooled it
24.4field-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

463 citing papers in PubMed, 2 syntheses or guidelines pooled it, 736 citations in OpenAlex.

  1. Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023
    Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Human cardiovascular organoids: Biomedical applications and ethical challenges.American heart journal plus : cardiology research and practice · 2026
    Review
  6. Article
  7. Article
  8. Review
  9. Article
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  11. Review
  12. Article
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  17. Circumferential strain recovery after human cardiomyocyte transplantation in minipigs using a novel frequency-based method for myocardial tagging quantification.Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance · 2026
    Article
  18. Review
  19. Article
  20. Article

403 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

4 authors at 1 institution in 1 country.

Scott D LundyDepartments of Bioengineering, University of Washington, Seattle, Washington, USA.
Wei-Zhong Zhu
Michael Regnier
Michael A Laflamme
California Institute for Regenerative Medicine · US

Funding

University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
Vascularization and Growth of Human Myocardial GraftsP01HL094374 · NHLBI · UNIVERSITY OF WASHINGTON · PI MACLELLAN, WILLIAM ROBB · 2010 to 2014
$14.5M
Engineered Cardiac Morphogenesis-Stem Cells and ScaffoldsR01HL064387 · NHLBI · UNIVERSITY OF WASHINGTON · PI RATNER, BUDDY D · 2006 to 2010
$10.2M
CARDIOVASCULAR RESEARCH TRAINING PROGRAMT32HL007828 · NHLBI · UNIVERSITY OF WASHINGTON · PI Francis Kim, Farid Moussavi-Harami · 1997 to 2026
$10.2M
EFFECT OF R1R2 OVER-EXPRESSION ON CARDIAC FUNCTIONR01HL111197 · NHLBI · UNIVERSITY OF WASHINGTON · PI REGNIER, MICHAEL · 2012 to 2015
$2.3M
Myocardium and Conduction System from ESCsK08HL080431 · NHLBI · UNIVERSITY OF WASHINGTON · PI LAFLAMME, MICHAEL ALAN · 2005 to 2009
$628k
Calcium-independent enhancement of contractility in normal and failing cardiomyocR21HL091368 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E, REGNIER, MICHAEL · 2008 to 2009
$429k
NHLBI NIH HHS K08-HL80431NHLBI NIH HHS P01-HL094374NHLBI NIH HHS R01-HL064387NHLBI NIH HHS R01-HL111197NHLBI NIH HHS R21-HL091368NHLBI NIH HHS U01-HL09997NIGMS NIH HHS T32-GM 7266-37
6 · The paper itself

Abstract

Despite preclinical studies demonstrating the functional benefit of transplanting human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) into damaged myocardium, the ability of these immature cells to adopt a more adult-like cardiomyocyte (CM) phenotype remains uncertain. To address this issue, we tested the hypothesis that prolonged in vitro culture of human embryonic stem cell (hESC)- and human induced pluripotent stem cell (hiPSC)-derived CMs would result in the maturation of their structural and contractile properties to a more adult-like phenotype. Compared to their early-stage counterparts (PSC-CMs after 20-40 days of in vitro differentiation and culture), late-stage hESC-CMs and hiPSC-CMs (80-120 days) showed dramatic differences in morphology, including increased cell size and anisotropy, greater myofibril density and alignment, sarcomeres visible by bright-field microscopy, and a 10-fold increase in the fraction of multinucleated CMs. Ultrastructural analysis confirmed improvements in the myofibrillar density, alignment, and morphology. We measured the contractile performance of late-stage hESC-CMs and hiPSC-CMs and noted a doubling in shortening magnitude with slowed contraction kinetics compared to the early-stage cells. We then examined changes in the calcium-handling properties of these matured CMs and found an increase in calcium release and reuptake rates with no change in the maximum amplitude. Finally, we performed electrophysiological assessments in hESC-CMs and found that late-stage myocytes have hyperpolarized maximum diastolic potentials, increased action potential amplitudes, and faster upstroke velocities. To correlate these functional changes with gene expression, we performed qPCR and found a robust induction of the key cardiac structural markers, including β-myosin heavy chain and connexin-43, in late-stage hESC-CMs and hiPSC-CMs. These findings suggest that PSC-CMs are capable of slowly maturing to more closely resemble the phenotype of adult CMs and may eventually possess the potential to regenerate the lost myocardium with robust de novo force-producing tissue.

Indexed as

Action PotentialsBiomarkersCalciumCell DifferentiationCells, CulturedConnexin 43Embryonic Stem CellsGene ExpressionHumansInduced Pluripotent Stem CellsMyocytes, CardiacMyofibrilsPatch-Clamp TechniquesTime FactorsVentricular MyosinsBiomarkersCalciumConnexin 43Ventricular Myosins

Identifiers

PMID23461462
PMCPMC3699903
OpenAlexW2134406150

What OpenQuestion holds

Textmetadata
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.