Vascular cells improve functionality of human cardiac organoids
Open accessAbstract
Crosstalk between cardiac cells is critical for heart performance. Here we show that vascular cells within human cardiac organoids (hCOs) enhance their maturation, force of contraction, and utility in disease modeling. Herein we optimize our protocol to generate vascular populations in addition to epicardial, fibroblast, and cardiomyocyte cells that self-organize into in-vivo-like structures in hCOs. We identify mechanisms of communication between endothelial cells, pericytes, fibroblasts, and cardiomyocytes that ultimately contribute to cardiac organoid maturation. In particular, (1) endothelial-derived LAMA5 regulates expression of mature sarcomeric proteins and contractility, and (2) paracrine platelet-derived growth factor receptor β (PDGFRβ) signaling from vascular cells upregulates matrix deposition to augment hCO contractile force. Finally, we demonstrate that vascular cells determine the magnitude of diastolic dysfunction caused by inflammatory factors and identify a paracrine role of endothelin driving dysfunction. Together this study highlights the importance and role of vascular cells in organoid models.
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Coculture may improve hCM survival and limited proliferation, increasing the number of functional cardiomyocytes.
“In addition, coculture may improve hCM survival and limited proliferation, increasing the number of functional cardiomyocytes.[ 57 , 58 , 59 ]”
From Engineered in vitro multi-cell type ventricle model generates long-term pulsatile flow and modulates cardiac output in response to cardioactive drugs (2025) · cites this paper as [57]
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- Authors
- Voges, H. K., Foster, S. R., Reynolds, L., Parker, B. L., Devilée, L., Quaife-Ryan, G. A., Fortuna, P. R. J., Mathieson, E., Fitzsimmons, R., Lor, M., Batho, C., Reid, J., Pocock, M., Friedman, C. E., Mizikovsky, D., Francois, M., Palpant, N. J., Needham, E. J., Peralta, M., Monte-Nieto, G. D., Jones, L. K., Smyth, I. M., Mehdiabadi, N. R., Bolk, F., Janbandhu, V., Yao, E., Harvey, R. P., Chong, J. J. H., Elliott, D. A., Stanley, E. G., Wiszniak, S., Schwarz, Q., James, D. E., Mills, R. J., Porrello, E. R., & Hudson, J. E.
- Affiliations
- Royal Children's Hospital (AU)
- QIMR Berghofer Medical Research Institute (AU)
- The University of Sydney (AU)
- The University of Queensland (AU)
- Australian Regenerative Medicine Institute (AU)
- Monash University (AU)
- Victor Chang Cardiac Research Institute (AU)
- South Australia Pathology (AU)
- Corresponding author
- Porrello, Enzo R.
- Hudson, James E.
- ORCID
- Voges, Holly K.
- Foster, Simon R.
- Reynolds, Liam
- Parker, Benjamin L.
- Devilée, Lynn
- Quaife-Ryan, Gregory A.
- Fortuna, Patrick R.J.
- Fitzsimmons, Rebecca
- Lor, Mary
- Batho, Christopher
- Reid, Janice
- Pocock, Mark
- Friedman, Clayton E.
- Mizikovsky, Dalia
- Palpant, Nathan J.
- Needham, Elise J.
- Peralta, Marina
- Smyth, Ian M.
- Mehdiabadi, Neda R.
- Janbandhu, Vaibhao
- Yao, Ernestene
- Harvey, Richard P.
- Chong, James J.H.
- Elliott, David A.
- Stanley, Edouard G.
- Wiszniak, Sophie
- Schwarz, Quenten
- James, David E.
- Mills, Richard J.
- Porrello, Enzo R.
- Hudson, James E.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2023-05
- Volume
- 42
- Issue
- 5
- Pages
- 112322
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W4367188943
- Cited by
- 139
- References
- 11
- Citations by year
- 2026: 38 · 2025: 52 · 2024: 36 · 2023: 13
- FWCI
- 12.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- UniSA Research Outputs Repository (University of South Australia) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by-nc-nd)
- Funders
- National Health and Medical Research Council
- National Heart Foundation of Australia
- University of Queensland
- Queensland Health
- State Government of Victoria
- Novo Nordisk Fonden (NNF21CC0073729)
- Royal Children's Hospital Foundation
- QIMR Berghofer Medical Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- vascular cells, endothelial cells, pericytes, cardiomyocytes, fibroblasts, organoid maturation, contractility, sarcomeric proteins, LAMA5, PDGFRβ signaling, extracellular matrix deposition, diastolic dysfunction, endothelin, paracrine signaling, disease modeling
- MeSH terms
- Humans, Organoids, Signal Transduction, Pericytes, Myocytes, Cardiac, Endothelial Cells
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