ArticleCardiovascular research2013
Derivation and maturation of synthetic and contractile vascular smooth muscle cells from human pluripotent stem cells.
Article in Cardiovascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 152 citations in OpenAlex.
- Investigational New Drug-enabling studies in a human vessel-chip: Are we there yet?Bioengineering & translational medicine · 2026Review
- uPAR deficiency triggers TGFβ1-mediated fibrotic remodeling in a cardiac perivascular-like microenvironment.Stem cell research & therapy · 2026Article
- Review
- La Ribonucleoprotein 7 Protects Vascular Smooth Muscle Cell Contractile Phenotype in CKD by Coupling with P300.Journal of the American Society of Nephrology : JASN · 2025Article
- Orphan receptor GPR153 facilitates vascular damage responses by modulating cAMP levels, YAP/TAZ signaling, and NF-κB activation.Nature communications · 2025Article
- Rapamycin reduces mineral density and promotes beneficial vascular remodeling in a murine model of severe medial arterial calcification.American journal of physiology. Heart and circulatory physiology · 2025Article
- Rapamycin Reduces Mineral Density and Promotes Beneficial Vascular Remodeling in a Murine Model of Severe Medial Arterial Calcification.bioRxiv : the preprint server for biology · 2025Article
- Next-Gen Therapeutics: Pioneering Drug Discovery with iPSCs, Genomics, AI, and Clinical Trials in a Dish.Annual review of pharmacology and toxicology · 2025Review
- SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection.Nature communications · 2024Article
- Use of iPSC-Derived Smooth Muscle Cells to Model Physiology and Pathology.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Primary Mouse Aortic Smooth Muscle Cells Exhibit Region- and Sex-Dependent Biological Responses In Vitro.Journal of biomechanical engineering · 2024Article
- Sonodynamic therapy for the treatment of atherosclerosis.Journal of pharmaceutical analysis · 2024Review
- The challenges and prospects of smooth muscle tissue engineering.Regenerative medicine · 2024Review
- Advances in the differentiation of pluripotent stem cells into vascular cells.World journal of stem cells · 2024Review
- Elucidating VSMC phenotypic transition mechanisms to bridge insights into cardiovascular disease implications.Frontiers in cardiovascular medicine · 2024Review
- Effect of Mechanical Stimuli on the Phenotypic Plasticity of Induced Pluripotent Stem-Cell-Derived Vascular Smooth Muscle Cells in a 3D Hydrogel.ACS applied bio materials · 2023Article
- Direct differentiation of human pluripotent stem cells into vascular network along with supporting mural cells.APL bioengineering · 2023Article
- Comparative study of differentiating human pluripotent stem cells into vascular smooth muscle cells in hydrogel-based culture methods.Regenerative therapy · 2023Article
- Ecto-5'-nucleotidase (Nt5e/CD73)-mediated adenosine signaling attenuates TGFβ-2 induced elastin and cellular contraction.American journal of physiology. Cell physiology · 2023Article
- Engineering Spatiotemporal Control in Vascularized Tissues.Bioengineering (Basel, Switzerland) · 2022Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
aimsEmbryonic vascular smooth muscle cells (vSMCs) have a synthetic phenotype; in adults, they commit to the mature contractile phenotype. Research shows that human pluripotent stem cells (hPSCs) differentiate into vSMCs, but nobody has yet documented their maturation into the synthetic or contractile phenotypes. This study sought to control the fate decisions of hPSC derivatives to guide their maturation towards a desired phenotype. METHODS AND
resultsThe long-term differentiation of hPSCs, including the integration-free-induced PSC line, in high serum with platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-β1, allowed us to induce the synthetic vSMC (Syn-vSMC) phenotype with increased extracellular matrix (ECM) protein expression and reduced expression of contractile proteins. By monitoring the expression of two contractile proteins, smooth muscle myosin heavy chain (SMMHC) and elastin, we show that serum starvation and PDGF-BB deprivation caused maturation towards the contractile vSMC (Con-vSMC) phenotype. Con-vSMCs differ distinctively from Syn-vSMC derivatives in their condensed morphology, prominent filamentous arrangement of cytoskeleton proteins, production and assembly of elastin, low proliferation, numerous and active caveolae, enlarged endoplasmic reticulum, and ample stress fibres and bundles, as well as their high contractility. When transplanted subcutaneously into nude mice, the human Con-vSMCs aligned next to the host's growing functional vasculature, with occasional circumferential wrapping and vascular tube narrowing.
conclusionWe control hPSC differentiation into synthetic or contractile phenotypes by using appropriate concentrations of relevant factors. Deriving Con-vSMCs from an integration-free hiPSC line may prove useful for regenerative therapy involving blood vessel differentiation and stabilization.
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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.