Development of a human cardiac organoid injury model reveals innate regenerative potential
Abstract
The adult human heart possesses a limited regenerative potential following an ischemic event, and undergoes a number of pathological changes in response to injury. Although cardiac regeneration has been documented in zebrafish and neonatal mouse hearts, it is currently unknown whether the immature human heart is capable of undergoing complete regeneration. Combined progress in pluripotent stem cell differentiation and tissue engineering has facilitated the development of human cardiac organoids (hCOs), which resemble fetal heart tissue and can be used to address this important knowledge gap. This study aimed to characterize the regenerative capacity of immature human heart tissue in response to injury. Following cryoinjury with a dry ice probe, hCOs exhibited an endogenous regenerative response with full functional recovery 2 weeks after acute injury. Cardiac functional recovery occurred in the absence of pathological fibrosis or cardiomyocyte hypertrophy. Consistent with regenerative organisms and neonatal human hearts, there was a high basal level of cardiomyocyte proliferation, which may be responsible for the regenerative capacity of the hCOs. This study suggests that immature human heart tissue has an intrinsic capacity to regenerate.
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Cardiac organoids have played an important role in understanding cardiac diseases such as arrhythmia and cardiac repair after injury.
“Cardiac organoids have played an important role in understanding cardiac diseases such as arrhythmia and cardiac repair after injury [56,57].”
From Utility of iPSC-Derived Cells for Disease Modeling, Drug Development, and Cell Therapy (2022) · cites this paper as [57]
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“Cardiac organoids have played an important role in understanding cardiac diseases such as arrhythmia and cardiac repair after injury [56,57].”
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- Authors
- Voges, H. K., Mills, R. J., Elliott, D. A., Parton, R. G., Porrello, E. R., & Hudson, J. E.
- Affiliations
- The University of Queensland (AU)
- Royal Children's Hospital (AU)
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2017-01-01
- Volume
- 144
- Issue
- 6
- Pages
- 1118-1127
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2587731622
- Cited by
- 196
- References
- 6
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 22 · 2023: 28 · 2022: 30 · 2021: 39 · 2020: 27 · 2019: 12 · 2018: 13 · 2017: 6
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Health and Medical Research Council
- National Heart Foundation of Australia
- Stem Cells Australia
- Australian Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- cardiac regeneration, cryoinjury, cardiomyocyte proliferation, functional recovery, fibrosis, cardiomyocyte hypertrophy, pluripotent stem cell differentiation, tissue engineering
- MeSH terms
- Adult, Cell Differentiation, Cell Line, Freezing, Heart, Heart Function Tests, Heart Injuries, Humans, Hypertrophy, Models, Biological, Myocardial Contraction, Myocardium, Organoids, Regeneration, Cell Death, Recovery of Function, Myocytes, Cardiac, Cell Proliferation
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