Evidence map›Paper›PMID 32228120›Full record

ArticleCirculation research2020

In Situ Expansion, Differentiation, and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid.

Molly E Kupfer, Wei-Han Lin, Vasanth Ravikumar, Kaiyan Qiu, Lu Wang, Ling Gao, Didarul B Bhuiyan, Megan Lenz, Jeffrey Ai, Ryan R Mahutga and 5 more

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

Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
169citing papers in PubMed, 1 pooled it
15.2field-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

169 citing papers in PubMed, 1 synthesis or guideline pooled it, 314 citations in OpenAlex.

  1. Pooled it
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  5. Human cardiovascular organoids: Biomedical applications and ethical challenges.American heart journal plus : cardiology research and practice · 2026
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109 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Molly E Kupfer *From the Department of Biomedical Engineering (M.E.K., W.-H.L., D.B.B., M.L., J.A., R.R.M., E.G.T., B.M.O.), University of Minnesota-Twin Cities, Minneapolis.
Wei-Han Lin *From the Department of Biomedical Engineering (M.E.K., W.-H.L., D.B.B., M.L., J.A., R.R.M., E.G.T., B.M.O.), University of Minnesota-Twin Cities, Minneapolis.
Vasanth RavikumarDepartment of Electrical Engineering (V.R.), University of Minnesota-Twin Cities, Minneapolis.
Kaiyan QiuDepartment of Mechanical Engineering (K.Q., M.C.M.), University of Minnesota-Twin Cities, Minneapolis.
Lu WangDepartment of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham (L.W., L.G., J.Z.).
Ling GaoDepartment of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham (L.W., L.G., J.Z.).
Didarul B BhuiyanFrom the Department of Biomedical Engineering (M.E.K., W.-H.L., D.B.B., M.L., J.A., R.R.M., E.G.T., B.M.O.), University of Minnesota-Twin Cities, Minneapolis.
Megan LenzFrom the Department of Biomedical Engineering (M.E.K., W.-H.L., D.B.B., M.L., J.A., R.R.M., E.G.T., B.M.O.), University of Minnesota-Twin Cities, Minneapolis.
Jeffrey AiFrom the Department of Biomedical Engineering (M.E.K., W.-H.L., D.B.B., M.L., J.A., R.R.M., E.G.T., B.M.O.), University of Minnesota-Twin Cities, Minneapolis.
Ryan R MahutgaFrom the Department of Biomedical Engineering (M.E.K., W.-H.L., D.B.B., M.L., J.A., R.R.M., E.G.T., B.M.O.), University of Minnesota-Twin Cities, Minneapolis.
DeWayne TownsendLillehei Heart Institute (D.T., E.G.T., B.M.O.), University of Minnesota-Twin Cities, Minneapolis.
Jianyi ZhangDepartment of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham (L.W., L.G., J.Z.).
Michael C McAlpineDepartment of Mechanical Engineering (K.Q., M.C.M.), University of Minnesota-Twin Cities, Minneapolis.
Elena G TolkachevaFrom the Department of Biomedical Engineering (M.E.K., W.-H.L., D.B.B., M.L., J.A., R.R.M., E.G.T., B.M.O.), University of Minnesota-Twin Cities, Minneapolis.
Brenda M OgleFrom the Department of Biomedical Engineering (M.E.K., W.-H.L., D.B.B., M.L., J.A., R.R.M., E.G.T., B.M.O.), University of Minnesota-Twin Cities, Minneapolis.
University of Minnesota · USUniversity of Alabama at Birmingham · US

Funding

University of Alabama at Birmingham's Diabetes Research CenterP30DK079626 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BARBARA A GOWER · 2013 to 2026
$19.5M
TRAINING FOR FUTURE BIOTECHNOLOGY DEVELOPMENTT32GM008347 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SCHMIDT-DANNERT, CLAUDIA · 1990 to 2021
$11.0M
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
3D Printed Nano-Bionic OrgansDP2EB020537 · NIBIB · UNIVERSITY OF MINNESOTA · PI MCALPINE, MICHAEL · 2014 to 2019
$2.7M
Deciphering the Neonatal Cardiac Regenerative Potential and Regulators in Large AnimalsR01HL149137 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SADEK, HESHAM, ZANGI, LIOR · 2019 to 2022
$2.5M
Extracellular matrix regulation of differentiation via modulation of ILK: application to 3D bioprinting of cardiac tissueR01HL137204 · NHLBI · UNIVERSITY OF MINNESOTA · PI MCALPINE, MICHAEL, OGLE, BRENDA M · 2017 to 2020
$1.7M
NHLBI NIH HHS R01 HL131017NHLBI NIH HHS R01 HL137204NHLBI NIH HHS R01 HL149137NIBIB NIH HHS DP2 EB020537NIDDK NIH HHS P30 DK079626NIGMS NIH HHS T32 GM008347
6 · The paper itself

Abstract

rationaleOne goal of cardiac tissue engineering is the generation of a living, human pump in vitro that could replace animal models and eventually serve as an in vivo therapeutic. Models that replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be achieved using 3-dimensional bioprinting. Yet, inclusion of contiguous, living muscle to support pump function has not been achieved. This is largely due to the challenge of attaining high densities of cardiomyocytes-a notoriously nonproliferative cell type. An alternative strategy is to print with human induced pluripotent stem cells, which can proliferate to high densities and fill tissue spaces, and subsequently differentiate them into cardiomyocytes in situ.

objectiveTo develop a bioink capable of promoting human induced pluripotent stem cell proliferation and cardiomyocyte differentiation to 3-dimensionally print electromechanically functional, chambered organoids composed of contiguous cardiac muscle. METHODS AND

resultsWe optimized a photo-crosslinkable formulation of native ECM (extracellular matrix) proteins and used this bioink to 3-dimensionally print human induced pluripotent stem cell-laden structures with 2 chambers and a vessel inlet and outlet. After human induced pluripotent stem cells proliferated to a sufficient density, we differentiated the cells within the structure and demonstrated function of the resultant human chambered muscle pump. Human chambered muscle pumps demonstrated macroscale beating and continuous action potential propagation with responsiveness to drugs and pacing. The connected chambers allowed for perfusion and enabled replication of pressure/volume relationships fundamental to the study of heart function and remodeling with health and disease.

conclusionsThis advance represents a critical step toward generating macroscale tissues, akin to aggregate-based organoids, but with the critical advantage of harboring geometric structures essential to the pump function of cardiac muscle. Looking forward, human chambered organoids of this type might also serve as a test bed for cardiac medical devices and eventually lead to therapeutic tissue grafting.

Indexed as

Cell DifferentiationAction PotentialsBioprintingCell ProliferationCells, CulturedExtracellular Matrix ProteinsHumansInduced Pluripotent Stem CellsMyocardial ContractionMyocytes, CardiacOrganoidsTissue EngineeringExtracellular Matrix Proteinsbiocompatible materialsbioprintingextracellular matrix proteinsinduced pluripotent stem cellsmyocytes, cardiacorganoidstissue engineering

Identifiers

PMID32228120
PMCPMC8210857
OpenAlexW3014021096

What OpenQuestion holds

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Read underepoch 390

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.