ArticleStem cells (Dayton, Ohio)2016
Hyaluronan Is Crucial for Stem Cell Differentiation into Smooth Muscle Lineage.
Article in Stem cells (Dayton, Ohio), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 21 papers.
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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
21 citing papers in PubMed, 44 citations in OpenAlex.
- Proteoglycans and glycosaminoglycans: critical regulators in angiogenesis, vasculogenesis, and vascularized tissue engineering.Angiogenesis · 2025Review
- Biomimetic Hyaluronan Binding Biomaterials to Capture the Complex Regulation of Hyaluronan in Tissue Development and Function.Biomimetics (Basel, Switzerland) · 2024Review
- Glycosaminoglycans' Ability to Promote Wound Healing: From Native Living Macromolecules to Artificial Biomaterials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Age related changes in hyaluronan expression leads to Meibomian gland dysfunction.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Free-aldehyde neutralized and oligohyaluronan loaded bovine pericardium with improved anti-calcification and endothelialization for bioprosthetic heart valves.Frontiers in bioengineering and biotechnology · 2023Article
- Article
- The investigation of diverse physiological and therapeutic impact of cellular-based products derived from human cumulus cells.Turkish journal of biology = Turk biyoloji dergisi · 2022Article
- Protective Effects of a Hyaluronan-Binding Peptide (P15-1) on Mesenchymal Stem Cells in an Inflammatory Environment.International journal of molecular sciences · 2021Article
- Natural Presentation of Glycosaminoglycans in Synthetic Matrices for 3D Angiogenesis Models.Frontiers in cell and developmental biology · 2021Article
- Diverse Roles for Hyaluronan and Hyaluronan Receptors in the Developing and Adult Nervous System.International journal of molecular sciences · 2020Review
- Hyaluronic Acid: Redefining Its Role.Cells · 2020Review
- Article
- A Hyaluronan-binding Peptide (P15-1) Reduces Inflammatory and Catabolic Events in IL-1β-treated Human Articular Chondrocytes.Scientific reports · 2020Article
- Coronary artery mechanics induces human saphenous vein remodellingTheranostics · 2020Article
- Homozygous receptors for insulin and not IGF-1 accelerate intimal hyperplasia in insulin resistance and diabetes.Nature communications · 2019Article
- Dissecting the Dual Nature of Hyaluronan in the Tumor Microenvironment.Frontiers in immunology · 2019Review
- Hyaluronan negatively regulates vascular calcification involving BMP2 signaling.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Concise Review: Stem/Progenitor Cell Proteoglycans Decorated with 7-D-4, 4-C-3, and 3-B-3(-) Chondroitin Sulfate Motifs Are Morphogenetic Markers of Tissue Development.Stem cells (Dayton, Ohio) · 2018Review
- Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering.Biomaterials · 2017Article
- Transdifferentiated Human Vascular Smooth Muscle Cells are a New Potential Cell Source for Endothelial Regeneration.Scientific reports · 2017Article
Corrections and comments
- Expression of concern
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Deciphering the extracellular signals that regulate SMC differentiation from stem cells is vital to further our understanding of the pathogenesis of vascular disease and for development of cell-based therapies and tissue engineering. Hyaluronan (HA) has emerged as an important component of the stem cell niche, however its role during stem cell differentiation is a complicated and inadequately defined process. This study aimed to investigate the role of HA in embryonic stem cell (ESC) differentiation toward a SMC lineage. ESCs were seeded on collagen-IV in differentiation medium to generate ESC-derived SMCs (esSMCs). Differentiation coincided with increased HA synthase (HAS) 2 expression, accumulation of extracellular HA and its assembly into pericellular matrices. Inhibition of HA synthesis by 4-methylumbelliferone (4MU), removal of the HA coat by hyaluronidase (HYAL) or HAS2 knockdown led to abrogation of SMC gene expression. HA activates ERK1/2 and suppresses EGFR signaling pathways via its principle receptor, CD44. EGFR inactivation coincided with increased binding to CD44, which was further augmented by addition of high molecular weight (HMW)-HA either exogenously or via HAS2 overexpression through adenoviral gene transfer. HMW-HA-stimulated esSMCs displayed a functional role in vascular tissue engineering ex vivo, vasculogenesis in a matrigel plug model and SMC accumulation in neointimal lesions of vein grafts in mice. These findings demonstrate that HAS2-induced HA synthesis and organization drives ESC-SMC differentiation. Thus, remodeling of the HA microenvironment is a critical step in directing stem cell differentiation toward a vascular lineage, highlighting HA as a potential target for treatment of vascular diseases. Stem Cells 2016;34:1225-1238.
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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.