Evidence map›Paper›PMID 29233823›Full record

ArticleCirculation2018

Large Cardiac Muscle Patches Engineered From Human Induced-Pluripotent Stem Cell-Derived Cardiac Cells Improve Recovery From Myocardial Infarction in Swine.

Ling Gao, Zachery R Gregorich, Wuqiang Zhu, Saidulu Mattapally, Yasin Oduk, Xi Lou, Ramaswamy Kannappan, Anton V Borovjagin, Gregory P Walcott, Andrew E Pollard and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 288 papers.

0numbers the graph read from it
0cells of the map it votes in
288citing papers in PubMed
32.2field-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

288 citing papers in PubMed, 459 citations in OpenAlex.

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228 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

15 authors at 3 institutions in 5 countries.

Ling GaoDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Zachery R GregorichDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison (Z.R.G., Y.G.).
Wuqiang ZhuDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Saidulu MattapallyDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Yasin OdukDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Xi LouDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Ramaswamy KannappanDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Anton V BorovjaginDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Gregory P WalcottDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Andrew E PollardDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Vladimir G FastDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Xinyang HuSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (X.H.).
Steven G LloydDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.).
Ying GeDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison (Z.R.G., Y.G.).
Jianyi ZhangDepartment of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham (L.G., W.Z., S.M., Y.O., X.LO., R.K., A.V.B., G.P.W., A.E.P., V.G.F., S.G.L., J.Z.). jayzhang@uab.edu.
Girls Incorporated · USRegenerative Medicine Institute · MXSecond Affiliated Hospital of Zhejiang University · CN

Funding

University of Alabama at Birmingham's Diabetes Research CenterP30DK079626 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Stuart J Frank · 2013 to 2026
$19.5M
MECHANISMS OF HYPERTENSION AND CARDIOVASCULAR DISEASEST32HL007457 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Martin E Young · 1985 to 2026
$8.6M
Integrated Cellular and Tissue Engineering for Ischemic Heart DiseaseU01HL134764 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BURSAC, NENAD, KAMP, TIMOTHY J. · 2016 to 2022
$7.7M
Supplement of HL131017: Myocardial remuscularization by cardiac patch delivery of epicardial FSTL1 and CCND2 overexpressing cardiomyocytesR01HL131017 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SERPOOSHAN, VAHID, ZHANG, JIANYI · 2016 to 2025
$5.8M
Endogenous and exogenous mechanisms that promote myocardial remuscularization in post infarction LV remodelingR01HL114120 · NHLBI · UNIVERSITY OF MINNESOTA · PI ZHANG, JIANYI · 2012 to 2021
$5.6M
Stem Cells For Myocardial Repair: A Large Bore Magnet StudyR01HL095077 · NHLBI · UNIVERSITY OF MINNESOTA · PI ZHANG, JIANYI · 2009 to 2017
$3.8M
Deciphering Myofilament Modifications in Ischemic CardiomyopathyR01HL109810 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2013 to 2024
$3.5M
Mesenchymal Stem Cell Exosome in Efferocytosis of Apoptotic Cardiomyocytes and Repair after Myocardial IschemiaR01HL138023 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KRISHNAMURTHY, PRASANNA, ZHANG, JIANYI · 2018 to 2021
$2.6M
Ultra High Resolution Mass Spectrometer for Biomedical ResearchS10OD018475 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2015 to 2015
$2.0M
A systems biology approach to understanding the role of myofilaments in cardiac regenerationF31HL128086 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GREGORICH, ZACHERY ROBERT · 2015 to 2016
$60k
NHLBI NIH HHS F31 HL128086NHLBI NIH HHS R01 HL095077NHLBI NIH HHS R01 HL109810NHLBI NIH HHS R01 HL114120NHLBI NIH HHS R01 HL131017NHLBI NIH HHS R01 HL138023NHLBI NIH HHS T32 HL007457NHLBI NIH HHS U01 HL134764NIDDK NIH HHS P30 DK079626NIH HHS S10 OD018475
6 · The paper itself

Abstract

backgroundHere, we generated human cardiac muscle patches (hCMPs) of clinically relevant dimensions (4 cm × 2 cm × 1.25 mm) by suspending cardiomyocytes, smooth muscle cells, and endothelial cells that had been differentiated from human induced-pluripotent stem cells in a fibrin scaffold and then culturing the construct on a dynamic (rocking) platform.

methodsIn vitro assessments of hCMPs suggest maturation in response to dynamic culture stimulation. In vivo assessments were conducted in a porcine model of myocardial infarction (MI). Animal groups included: MI hearts treated with 2 hCMPs (MI+hCMP, n=13), MI hearts treated with 2 cell-free open fibrin patches (n=14), or MI hearts with neither experimental patch (n=15); a fourth group of animals underwent sham surgery (Sham, n=8). Cardiac function and infarct size were evaluated by MRI, arrhythmia incidence by implanted loop recorders, and the engraftment rate by calculation of quantitative polymerase chain reaction measurements of expression of the human Y chromosome. Additional studies examined the myocardial protein expression profile changes and potential mechanisms of action that related to exosomes from the cell patch.

resultsThe hCMPs began to beat synchronously within 1 day of fabrication, and after 7 days of dynamic culture stimulation, in vitro assessments indicated the mechanisms related to the improvements in electronic mechanical coupling, calcium-handling, and force generation, suggesting a maturation process during the dynamic culture. The engraftment rate was 10.9±1.8% at 4 weeks after the transplantation. The hCMP transplantation was associated with significant improvements in left ventricular function, infarct size, myocardial wall stress, myocardial hypertrophy, and reduced apoptosis in the periscar boarder zone myocardium. hCMP transplantation also reversed some MI-associated changes in sarcomeric regulatory protein phosphorylation. The exosomes released from the hCMP appeared to have cytoprotective properties that improved cardiomyocyte survival.

conclusionsWe have fabricated a clinically relevant size of hCMP with trilineage cardiac cells derived from human induced-pluripotent stem cells. The hCMP matures in vitro during 7 days of dynamic culture. Transplantation of this type of hCMP results in significantly reduced infarct size and improvements in cardiac function that are associated with reduction in left ventricular wall stress. The hCMP treatment is not associated with significant changes in arrhythmogenicity.

Indexed as

RegenerationAnimalsCell DifferentiationCells, CulturedDisease Models, AnimalEndothelial CellsGene Expression RegulationHumansInduced Pluripotent Stem CellsMyocardial InfarctionMyocardiumMyocytes, CardiacMyocytes, Smooth MuscleRecovery of FunctionStem Cell TransplantationSus scrofaheartmodels, animalmyocardial infarctionpluripotent stem cellstissue engineering

Identifiers

PMID29233823
PMCPMC5903991
OpenAlexW2774069831

What OpenQuestion holds

Textmetadata
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.