Cited by 593Pluripotent Stem Cells ResearchCongenital heart defects researchTissue Engineering and Regenerative Medicine

Cardioids reveal self-organizing principles of human cardiogenesis

Open access
Hofbauer, Pablo, Jahnel, Stefan M., Papai, Nora, Giesshammer, Magdalena, Deyett, Alison, Schmidt, Clara, Penc, Mirjam, Tavernini, Katherina +7 more·2021·Cell

Published version of a preprint

Abstract

Organoids capable of forming tissue-like structures have transformed our ability to model human development and disease. With the notable exception of the human heart, lineage-specific self-organizing organoids have been reported for all major organs. Here, we established self-organizing cardioids from human pluripotent stem cells that intrinsically specify, pattern, and morph into chamber-like structures containing a cavity. Cardioid complexity can be controlled by signaling that instructs the separation of cardiomyocyte and endothelial layers and by directing epicardial spreading, inward migration, and differentiation. We find that cavity morphogenesis is governed by a mesodermal WNT-BMP signaling axis and requires its target HAND1, a transcription factor linked to developmental heart chamber defects. Upon cryoinjury, cardioids initiated a cell-type-dependent accumulation of extracellular matrix, an early hallmark of both regeneration and heart disease. Thus, human cardioids represent a powerful platform to mechanistically dissect self-organization, congenital heart defects and serve as a foundation for future translational research.

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Crossref · 10.1016/j.cell.2021.04.034

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  • These cardioids relied heavily on complex growth factor mixtures, co-culture approaches to include epicardial clusters, and independent differentiation protocols.

    “While demonstrating a large leap in self-assembling capabilities, these cardioids still relied heavily on complex growth factor mixtures, co-culture approaches to include epicardial clusters, and independent differentiation protocols to achieve their final results.”
  • Cardioids have been reported with a large internal chamber, relevant cardiac cell lineages and single cell transcriptomic analysis.

    “cardioids (an alternative nomenclature for heart or cardiac organoids) have been reported with a large internal chamber, relevant cardiac cell lineages and single cell transcriptomic analysis20.”

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Authors
Hofbauer, P., Jahnel, S. M., Papai, N., Giesshammer, M., Deyett, A., Schmidt, C., Penc, M., Tavernini, K., Grdseloff, N., Meledeth, C., Ginistrelli, L. C., Ctortecka, C., Šalic, Š., Novatchkova, M., & Mendjan, S.
Affiliations
  • Institute of Molecular Biotechnology (AT)
  • Research Institute of Molecular Pathology (AT)
Corresponding author
Mendjan, Sasha
Venue
Cell
Publisher
Elsevier BV
Published
2021-06
Volume
184
Issue
12
Pages
3299-3317.e22
ISSN
0092-8674 (ISSN-L)
OpenAlex
W3161466741
Cited by
588
References
119
Citations by year
2026: 121 · 2025: 130 · 2024: 118 · 2023: 92 · 2022: 90 · 2021: 35 · 2020: 2
FWCI
26.74
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
Funders
FFG
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
cardioid, heart development, self-organization, human pluripotent stem cells, HAND1, extracellular matrix accumulation, cryoinjury, congenital heart disease, cardiac regeneration
MeSH terms
Homeobox Protein Nkx-2.5, Animals, Calcium, Cell Line, Chickens, Female, Fibroblasts, Heart, Humans, Male, Mesoderm, Models, Biological, Myocardium, Organoids, Extracellular Matrix Proteins, Cell Lineage, Bone Morphogenetic Proteins, Activins, Organogenesis, Pluripotent Stem Cells, Vascular Endothelial Growth Factor A, Endothelial Cells, Wnt Proteins, Basic Helix-Loop-Helix Proteins

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