Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors
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Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFβ1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties of the cardiomyocytes compared to co-culture with dermal fibroblasts. The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration.
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Co-culture with cardiac fibroblasts or endothelial cells influences cardiomyocyte maturation, hypertrophy, function, and gene expression.
“Similarly, co-culture with cardiac fibroblasts or endothelial cells has also been shown to influence cardiomyocyte maturation, hypertrophy, function and gene expression [26,27,28].”
From Utility of iPSC-Derived Cells for Disease Modeling, Drug Development, and Cell Therapy (2022) · cites this paper as [27]
The Results section, “Co-culture of hPSC-CFs effects hPSC-CM electrophysiology” (page not available), reports that co-culture with cardiac fibroblasts changes cardiomyocyte monolayer electrical function. The passages do not establish effects of endothelial-cell co-culture or effects on cardiomyocyte maturation, hypertrophy, or gene expression. (LLM, conf=0.86)
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Self-citation
- Authors
- Zhang, J., Tao, R., Campbell, K. F., Carvalho, J. L., Ruiz, E. C., Kim, G. C., Schmuck, E. G., Raval, A. N., da Rocha, A. M., Herron, T. J., Jalife, J., Thomson, J. A., & Kamp, T. J.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Michigan (US)
- Corresponding author
- Zhang, Jianhua
- Kamp, Timothy J.
- ORCID
- Venue
- Nature Communications
- Published
- 2019-05-20
- Volume
- 10
- Issue
- 1
- Pages
- 2238-2238
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6527555
- OpenAlex
- W2901646806
- Cited by
- 201
- References
- 71
- Citations by year
- 2026: 15 · 2025: 32 · 2024: 27 · 2023: 29 · 2022: 30 · 2021: 34 · 2020: 26 · 2019: 8
- FWCI
- 8.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- National Institutes of Health (NIH-R01, UL1TR000427)
- Institute for Clinical and Translational Research, University of Wisconsin, Madison (UL1TR000427)
- National Heart, Lung, and Blood Institute (U01HL134764, R01HL129798)
- National Center for Research Resources (S10RR025644)
- National Center for Advancing Translational Sciences
- 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 › Genetics › Mesenchymal stem cell research
- Keywords
- cardiac fibroblasts, human pluripotent stem cells, Wnt signaling, FGF signaling, myofibroblast transformation, TGF-β1, angiotensin II, extracellular matrix, cardiomyocyte electrophysiology, co-culture, cardiac regeneration, fibroblast differentiation
- MeSH terms
- Intravital Microscopy, Cell Differentiation, Cell Line, Fibroblasts, Heart, Humans, Microscopy, Fluorescence, Myocardium, Coculture Techniques, Dermis, Induced Pluripotent Stem Cells, Primary Cell Culture, Healthy Volunteers
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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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