Cited by 3293D Printing in Biomedical ResearchTissue Engineering and Regenerative MedicinePluripotent Stem Cells Research

The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index; 59 of the 78 sources its claims cite were checked for support.

In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid

Open access

Abstract

RATIONALE: One 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. OBJECTIVE: To 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 RESULTS: We 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. CONCLUSIONS: This 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.

Overview

Integrity signals

Registry

Crossref · 10.1161/circresaha.119.316155

Cites

63 of 63 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

65 Own result · 30 Own interpretation · 16 No basis given · 14 Partly supported · 8 No full text of the sources · 6 Supported · 3 Couldn’t confirm · 2 Own method · 1 Supported so far · 1 Mixed support · accuracy not yet measured

Show all 95 claims

  • It may state two separate claims as one. 41
  • Probably not a substantial claim. 10
  • The quote only partly states this claim. 1
51 of 51
  • The paper relies on this without support.

    Cardiomyocytes do not proliferate or migrate readily.

    “More specifically, cardiomyocytes do not proliferate or migrate readily.”
  • The paper relies on this without support.

    A high cell density is required for the formation of functional cell-cell junctions.

    “it is challenging to achieve the high cell density required for the formation of functional cell-cell junctions while maintaining the structural support needed for an enclosed chamber.”
  • The authors state this as an assumption.

    The pipetted disk used for cell-density estimation has a thickness of 1 mm.

    “Assuming a disk thickness of 1 mm”
  • The authors state this as an assumption.

    The average cell contains 6 pg of DNA.

    “If the average cell contains 6 pg of DNA”
  • The authors state this as an assumption.

    In the in silico model, the entire wall thickness is occupied by cells.

    “1) the entirety of the wall thickness is occupied by cells”
  • The authors state this as an assumption.

    In the in silico model, about half of the wall thickness, 600–650 μm, is occupied by cells.

    “2) approximately half of the wall thickness (600–650 μm) is occupied by cells”
  • The authors state this as an assumption.

    In the in silico model, cellularization is confined to the outer 200–250 μm of the structure.

    “3) the cellularization is limited to the outer 200–250 μm of the structure”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

2 of 2

Citations

Cites

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Metadata

Authors
Kupfer, M. E., Lin, W.-H., Ravikumar, V., Qiu, K., Wang, L., Gao, L., Bhuiyan, D. B., Lenz, M., Ai, J., Mahutga, R. R., Townsend, D., Zhang, J., McAlpine, M. C., Tolkacheva, E. G., & Ogle, B. M.
Affiliations
  • University of Minnesota (US)
  • University of Alabama at Birmingham (US)
Venue
Circulation Research
Published
2020-07-03
Volume
127
Issue
2
Pages
207-224
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
OpenAlex
W3014021096
Cited by
329
References
64
Citations by year
2026: 45 · 2025: 55 · 2024: 63 · 2023: 51 · 2022: 58 · 2021: 47 · 2020: 10
FWCI
13.03
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL137204, R01HL149137, R01HL131017)
  • National Institute of General Medical Sciences (T32GM008347)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK079626)
  • National Institute of Biomedical Imaging and Bioengineering (DP2EB020537)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
3D bioprinting, human induced pluripotent stem cells, cardiomyocyte differentiation, in situ differentiation, bioinks, extracellular matrix, electromechanical coupling, action potential propagation, cardiac tissue engineering, cardiac remodeling, tissue grafting
MeSH terms
Action Potentials, Cell Differentiation, Cells, Cultured, Humans, Myocardial Contraction, Organoids, Extracellular Matrix Proteins, Tissue Engineering, Myocytes, Cardiac, Cell Proliferation, Induced Pluripotent Stem Cells, Bioprinting

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (prompt extract-v3).

A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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