Evidence map›Paper›PMID 21597009›Full record

ArticleCirculation research2011

Growth of engineered human myocardium with mechanical loading and vascular coculture.

Nathaniel L Tulloch, Veronica Muskheli, Maria V Razumova, F Steven Korte, Michael Regnier, Kip D Hauch, Lil Pabon, Hans Reinecke, Charles E Murry

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 361 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
361citing papers in PubMed, 3 pooled it
49.5field-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

361 citing papers in PubMed, 3 syntheses or guidelines pooled it, 667 citations in OpenAlex.

  1. Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023
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  10. Mechanisms and Therapeutic Potential of Human Cardiomyocyte Proliferation.Journal of cardiovascular development and disease · 2026
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301 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 2 institutions in 3 countries.

Nathaniel L TullochMolecular and Cellular Biology Program, Center for Cardiovascular Biology, Institute for Stem Cell and Regenerative Medicine, University of Washington, 815 Mercer St., Seattle, WA 98109, USA.
Veronica Muskheli
Maria V Razumova
F Steven Korte
Michael Regnier
Kip D Hauch
Lil Pabon
Hans Reinecke
Charles E Murry
Maine Farmland Trust · USInstitute for Stem Cell Biology and Regenerative Medicine · IN

Funding

Self Renewal and Differentiation of Human Embryonic Stem CellsP01GM081619 · NIGMS · UNIVERSITY OF WASHINGTON · PI WARE, CAROL B · 2007 to 2017
$20.6M
Vascularization and Growth of Human Myocardial GraftsP01HL094374 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2010 to 2014
$14.5M
EXPERIMENTAL PATHOLOGY OF CARDIOVASCULAR DISEASET32HL007312 · NHLBI · UNIVERSITY OF WASHINGTON · PI MAJESKY, MARK W., SCHWARTZ, STEPHEN MARK · 1985 to 2019
$11.8M
Engineered Cardiac Morphogenesis-Stem Cells and ScaffoldsR01HL064387 · NHLBI · UNIVERSITY OF WASHINGTON · PI RATNER, BUDDY D · 2006 to 2010
$10.2M
Cell-Based Cardiac RepairR01HL084642 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2007 to 2014
$4.9M
MMPC: Diabetes and Diabectic ComplicationsU24DK076126 · NIDDK · UNIVERSITY OF WASHINGTON · PI LEBOEUF, RENEE C · 2006 to 2010
$4.8M
NHLBI NIH HHS P01 HL094374NHLBI NIH HHS P01HL094374NHLBI NIH HHS R01 HL064387NHLBI NIH HHS R01 HL084642NHLBI NIH HHS R01HL084642NHLBI NIH HHS R01HL64387NHLBI NIH HHS T32 HL007312NHLBI NIH HHS T32HL007312NIDDK NIH HHS U24 DK076126NIGMS NIH HHS P01 GM081619NIGMS NIH HHS P01GM81619
6 · The paper itself

Abstract

rationaleThe developing heart requires both mechanical load and vascularization to reach its proper size, yet the regulation of human heart growth by these processes is poorly understood.

objectiveWe seek to elucidate the responses of immature human myocardium to mechanical load and vascularization using tissue engineering approaches. METHODS AND

resultsUsing human embryonic stem cell and human induced pluripotent stem cell-derived cardiomyocytes in a 3-dimensional collagen matrix, we show that uniaxial mechanical stress conditioning promotes 2-fold increases in cardiomyocyte and matrix fiber alignment and enhances myofibrillogenesis and sarcomeric banding. Furthermore, cyclic stress conditioning markedly increases cardiomyocyte hypertrophy (2.2-fold) and proliferation rates (21%) versus unconditioned constructs. Addition of endothelial cells enhances cardiomyocyte proliferation under all stress conditions (14% to 19%), and addition of stromal supporting cells enhances formation of vessel-like structures by ≈10-fold. Furthermore, these optimized human cardiac tissue constructs generate Starling curves, increasing their active force in response to increased resting length. When transplanted onto hearts of athymic rats, the human myocardium survives and forms grafts closely apposed to host myocardium. The grafts contain human microvessels that are perfused by the host coronary circulation.

conclusionsOur results indicate that both mechanical load and vascular cell coculture control cardiomyocyte proliferation, and that mechanical load further controls the hypertrophy and architecture of engineered human myocardium. Such constructs may be useful for studying human cardiac development as well as for regenerative therapy.

Indexed as

Tissue EngineeringAnimalsAnimals, NewbornBiomechanical PhenomenaCell ProliferationCells, CulturedCoculture TechniquesEmbryonic Stem CellsEndothelial CellsExtracellular MatrixHumansMyocytes, CardiacPluripotent Stem CellsRatsRats, Inbred F344Stress, Mechanical

Identifiers

PMID21597009
PMCPMC3140796
OpenAlexW2163068618

What OpenQuestion holds

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LicenceTDM
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.