Endothelial Cells Direct Mesenchymal Stem Cells Toward a Smooth Muscle Cell Fate
Open accessAbstract
Under defined conditions, mesenchymal stem cells can differentiate into unique cell types, making them attractive candidates for cell-based disease therapies. Ischemic diseases would greatly benefit from treatments that include the formation of new blood vessels from mesenchymal stem cells. However, blood vessels are complex structures composed of endothelial cells and smooth muscle cells, and their assembly and function in a diseased environment is reliant upon joining with the pre-existing vasculature. Although endothelial cell/smooth muscle cell interactions are well known, how endothelial cells may influence mesenchymal stem cells and facilitate their differentiation has not been defined. Therefore, we sought to explore how endothelial cells might drive mesenchymal stem cells toward a smooth muscle fate. Our data show that cocultured endothelial cells induce smooth muscle cell differentiation in mesenchymal stem cells. Endothelial cells can promote a contractile phenotype, reduce proliferation, and enhance collagen synthesis and secretion. Our data show that Notch signaling is essential for endothelial cell-dependent differentiation, and this differentiation pathway is largely independent of growth factor signaling mechanisms.
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The increased cartilage and mesenchymal lineage formation in SKOs receiving ECFCs may be attributed to secretion of growth factors such as platelet-derived growth factor and transforming growth factor-β by ECFCs, which promote mesenchymal lineage differentiation.
“that may be attributed to the secretion of growth factors such as platelet‐derived growth factor and transforming growth factor‐β by ECFCs, that promote mesenchymal lineage differentiation.[ 69 , 70 , 71 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [69]
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Endothelial Notch signaling as a target for aortic valve calcificationPreprint
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- Authors
- Lin, C.-H., & Lilly, B.
- Affiliations
- Nationwide Children's Hospital (US)
- Corresponding author
- Lilly, Brenda
- Venue
- Stem Cells and Development
- Publisher
- SAGE Publications
- Published
- 2014-11
- Volume
- 23
- Issue
- 21
- Pages
- 2581-2590
- ISSN
- 1525-8165 (ISSN-L)
- 1547-3287
- 1557-8534
- PMC
- PMC4201243
- OpenAlex
- W2335134891
- Cited by
- 50
- References
- 26
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 8 · 2016: 4 · 2015: 6 · 2014: 2
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Stem Cells and Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Nationwide Children's Hospital
- Research Institute, Nationwide Children's Hospital
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- mesenchymal stem cells, endothelial cells, smooth muscle differentiation, Notch signaling, cell-cell interactions, cell therapy, angiogenesis, ischemic diseases, collagen synthesis, cell proliferation, contractile phenotype
- MeSH terms
- Receptor, Notch3, Cell Differentiation, Cells, Cultured, Humans, Immunohistochemistry, Muscle, Smooth, Vascular, Blotting, Western, Gene Expression, Cell Cycle Proteins, Coculture Techniques, Ki-67 Antigen, Cyclin D1, Reverse Transcriptase Polymerase Chain Reaction, Myocytes, Smooth Muscle, Endothelial Cells, Cell Proliferation, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors, Receptors, Notch, Cyclin D2, Mesenchymal Stem Cells, Human Umbilical Vein Endothelial Cells
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