ArticleStem cells translational medicine2013
Modeling and rescue of the vascular phenotype of Williams-Beuren syndrome in patient induced pluripotent stem cells.
Article in Stem cells translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- Modeling Williams syndrome from a neurodevelopmental perspective: recent advances, model-based translational insights and future directions.World journal of pediatrics : WJP · 2026Review
- Applications, challenges, and prospects of induced pluripotent stem cells for vascular disease.Molecules and cells · 2024Review
- Modelling phenotypes, variants and pathomechanisms of syndromic diseases in different systems.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2024Article
- Using Genomics to Identify Novel Therapeutic Targets for Aortic Disease.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells.Frontiers in cardiovascular medicine · 2024Review
- Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models.Genes · 2023Review
- Review
- Human Brain Models of Intellectual Disability: Experimental Advances and Novelties.International journal of molecular sciences · 2022Review
- JAGGED1/NOTCH3 activation promotes aortic hypermuscularization and stenosis in elastin deficiency.The Journal of clinical investigation · 2022Article
- Human Induced Pluripotent Stem Cell-Derived Vascular Cells: Recent Progress and Future Directions.Journal of cardiovascular development and disease · 2021Review
- Review
- The updated view on induced pluripotent stem cells for cardiovascular precision medicine.Pflugers Archiv : European journal of physiology · 2021Review
- Williams syndrome.Nature reviews. Disease primers · 2021Review
- Review
- In Vivo and In Vitro Genetic Models of Congenital Heart Disease.Cold Spring Harbor perspectives in biology · 2021Review
- Generation of Vascular Smooth Muscle Cells From Induced Pluripotent Stem Cells: Methods, Applications, and Considerations.Circulation research · 2021Review
- Modeling aortic diseases using induced pluripotent stem cells.Stem cells translational medicine · 2021Review
- Differentiation and Application of Human Pluripotent Stem Cells Derived Cardiovascular Cells for Treatment of Heart Diseases: Promises and Challenges.Frontiers in cell and developmental biology · 2021Review
- Human In Vitro Models for Assessing the Genomic Basis of Chemotherapy-Induced Cardiovascular Toxicity.Journal of cardiovascular translational research · 2020Review
- Everolimus Rescues the Phenotype of Elastin Insufficiency in Patient Induced Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Elastin haploinsufficiency in Williams-Beuren syndrome (WBS) leads to increased vascular smooth muscle cell (SMC) proliferation and stenoses. Our objective was to generate a human induced pluripotent stem (hiPS) cell model for in vitro assessment of the WBS phenotype and to test the ability of candidate agents to rescue the phenotype. hiPS cells were reprogrammed from skin fibroblasts of a WBS patient with aortic and pulmonary stenosis and healthy control BJ fibroblasts using four-factor retrovirus reprogramming and were differentiated into SMCs. Differentiated SMCs were treated with synthetic elastin-binding protein ligand 2 (EBPL2) (20 μg/ml) or the antiproliferative drug rapamycin (100 nM) for 5 days. We generated four WBS induced pluripotent stem (iPS) cell lines that expressed pluripotency genes and differentiated into all three germ layers. Directed differentiation of BJ iPS cells yielded an 85%-92% pure SMC population that expressed differentiated SMC markers, were functionally contractile, and formed tube-like structures on three-dimensional gel assay. Unlike BJ iPS cells, WBS iPS cells generated immature SMCs that were highly proliferative, showed lower expression of differentiated SMC markers, reduced response to the vasoactive agonists, carbachol and endothelin-1, impaired vascular tube formation, and reduced calcium flux. EBPL2 partially rescued and rapamycin fully rescued the abnormal SMC phenotype by decreasing the smooth muscle proliferation rate and enhancing differentiation and tube formation. WBS iPS cell-derived SMCs demonstrate an immature proliferative phenotype with reduced functional and contractile properties, thereby recapitulating the human disease phenotype. The ability of rapamycin to rescue the phenotype provides an attractive therapeutic candidate for patients with WBS and vascular stenoses.
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Registered trials
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