ArticleDevelopment (Cambridge, England)2015
Robust derivation of epicardium and its differentiated smooth muscle cell progeny from human pluripotent stem cells.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 84 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
84 citing papers in PubMed, 135 citations in OpenAlex.
- Signaling mechanisms and dynamics governing the myocardial-epicardial fate switch during human cardiogenesis.Science advances · 2026Article
- Generation of functional mesothelial cells from human iPSCs that restore peritoneal integrity in experimental peritoneal injury.Stem cell research & therapy · 2026Article
- Modeling embryonic heart vascular plexus development and sympathetic innervation on a human heart organoid.iScience · 2026Article
- Coordination of cardiogenesis in vivo and in vitro.Nature reviews. Molecular cell biology · 2026Review
- Advances in Epicardial Biology: Insights from Development, Regeneration, and Human Cardiac Organoids.Journal of cardiovascular development and disease · 2025Review
- Generation of mature epicardium derived from human-induced pluripotent stem cells via inhibition of mTOR signaling.Nature communications · 2025Article
- A retinoic acid:YAP1 signaling axis controls atrial lineage commitment.Cell reports · 2025Article
- AnMaterials today. Bio · 2025Article
- Epicardium-myocardium crosstalk orchestrates heart development.Frontiers in cell and developmental biology · 2025Review
- SMAD3 mediates the specification of human induced pluripotent stem cell-derived epicardium into progenitors for the cardiac pericyte lineage.Stem cell reports · 2024Article
- Transient Notch Activation Converts Pluripotent Stem Cell-Derived Cardiomyocytes Towards a Purkinje Fiber Fate.bioRxiv : the preprint server for biology · 2024Article
- Efficient and reproducible generation of human iPSC-derived cardiomyocytes and cardiac organoids in stirred suspension systems.Nature communications · 2024Article
- Use of iPSC-Derived Smooth Muscle Cells to Model Physiology and Pathology.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Revisiting Cardiac Biology in the Era of Single Cell and Spatial Omics.Circulation research · 2024Review
- Engineered Cardiac Microtissue Biomanufacturing Using Human Induced Pluripotent Stem Cell Derived Epicardial Cells.bioRxiv : the preprint server for biology · 2024Article
- Differentiation of Pluripotent Stem Cells for Disease Modeling: Learning from Heart Development.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Modeling cardiac fibroblast heterogeneity from human pluripotent stem cell-derived epicardial cells.Nature communications · 2023Article
- Harnessing stem cell and lineage reprogramming technology to treat cardiac fibrosis.Cell regeneration (London, England) · 2023Review
- Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease.Nature biotechnology · 2023Article
- Role and Mechanism of BMP4 in Regenerative Medicine and Tissue Engineering.Annals of biomedical engineering · 2023Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The epicardium has emerged as a multipotent cardiovascular progenitor source with therapeutic potential for coronary smooth muscle cell, cardiac fibroblast (CF) and cardiomyocyte regeneration, owing to its fundamental role in heart development and its potential ability to initiate myocardial repair in injured adult tissues. Here, we describe a chemically defined method for generating epicardium and epicardium-derived smooth muscle cells (EPI-SMCs) and CFs from human pluripotent stem cells (HPSCs) through an intermediate lateral plate mesoderm (LM) stage. HPSCs were initially differentiated to LM in the presence of FGF2 and high levels of BMP4. The LM was robustly differentiated to an epicardial lineage by activation of WNT, BMP and retinoic acid signalling pathways. HPSC-derived epicardium displayed enhanced expression of epithelial- and epicardium-specific markers, exhibited morphological features comparable with human foetal epicardial explants and engrafted in the subepicardial space in vivo. The in vitro-derived epicardial cells underwent an epithelial-to-mesenchymal transition when treated with PDGF-BB and TGFβ1, resulting in vascular SMCs that displayed contractile ability in response to vasoconstrictors. Furthermore, the EPI-SMCs displayed low density lipoprotein uptake and effective lowering of lipoprotein levels upon treatment with statins, similar to primary human coronary artery SMCs. Cumulatively, these findings suggest that HPSC-derived epicardium and EPI-SMCs could serve as important tools for studying human cardiogenesis, and as a platform for vascular disease modelling and drug screening.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.