ArticleStem cell research & therapy2019
Hypoxia promotes differentiation of adipose-derived stem cells into endothelial cells through demethylation of ephrinB2.
Article in Stem cell research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- A Review of the Therapeutic Efficacy and Safety of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Preclinical Models of Subacute and Chronic Myocardial Infarction.Journal of cardiovascular development and disease · 2026Review
- Revolutionizing Diabetic Foot Ulcer Management: Exploring the Therapeutic Potential of Natural Products.Current pharmaceutical design · 2026Review
- Angiogenic Potential of Small Extracellular Vesicles Produced by Stimulated Mesenchymal Stromal Cells Under Hypoxic Conditions.Journal of extracellular biology · 2026Article
- Review
- Optimal Sca-1-based procedure for purifying mouse adipose-derived mesenchymal stem cells with enhanced proliferative and differentiation potential.Frontiers in cell and developmental biology · 2025Article
- Application of adipose-derived stem cells in ischemic heart disease: theory, potency, and advantage.Frontiers in cardiovascular medicine · 2024Review
- The evolving functions of the vasculature in regulating adipose tissue biology in health and obesity.Nature reviews. Endocrinology · 2023Review
- Targeting DNA methylation and demethylation in diabetic foot ulcers.Journal of advanced research · 2023Review
- CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects.Scientific reports · 2023Article
- Construction of Bone Hypoxic Microenvironment Based on Bone-on-a-Chip Platforms.International journal of molecular sciences · 2023Review
- Secretome of Adipose-Derived Stem Cells Cultured in Platelet Lysate Improves Migration and Viability of Keratinocytes.International journal of molecular sciences · 2023Article
- Stem cell-mediated angiogenesis in skin tissue engineering and wound healing.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2022Review
- Vascular tissue engineering from human adipose tissue: fundamental phenotype of its resident microvascular endothelial cells and stromal/stem cells.Biomaterials and biosystems · 2022Article
- Article
- Tissue Engineered Neurovascularization Strategies for Craniofacial Tissue Regeneration.ACS applied bio materials · 2022Review
- Enhanced Microvasculature Formation and Patterning in iPSC-Derived Kidney Organoids Cultured in Physiological Hypoxia.Frontiers in bioengineering and biotechnology · 2022Article
- The role of BMP4 in adipose-derived stem cell differentiation: A minireview.Frontiers in cell and developmental biology · 2022Review
- Angiogenic Effects and Crosstalk of Adipose-Derived Mesenchymal Stem/Stromal Cells and Their Extracellular Vesicles with Endothelial Cells.International journal of molecular sciences · 2021Review
- The effect and molecular mechanism of hypoxia on proliferation and apoptosis of CD133+ renal stem cells.Bosnian journal of basic medical sciences · 2021Article
- The Angiogenic Potential of Mesenchymal Stem Cells from the Hair Follicle Outer Root Sheath.Journal of clinical medicine · 2021Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDelivery of endothelial cells into the ischemic tissue is emerging as an alternative approach in revascularization of injured tissues by means of angiogenesis to restore organ function. Adipose-derived stem cells (ASCs) are a readily accessible source of the mesenchymal stem cell with rapid expansion and multidifferentiation potential. The view has emerged that endothelial cells (ECs) differentiated from ASCs is a step forward for adult vascular repair in regenerative medicine and construction of the blood vessel by tissue engineering approach.
methodsIn this study, differentiation of human ASCs (hASCs) into vascular EC lineage was induced by combined treatment of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-4 (BMP4) under hypoxia condition. The expression of CD31, VEGF-R2, and VE-cadherin was determined by immunofluorescent staining, real-time PCR, and western blot analysis. These differentiated cells acquired functional characteristics of mature ECs as determined by their tube formation ability, DiI-ac-LDL uptake, and nitric oxide secretion in vitro. The methylation status in the proximal promoter CpGs was determined by bisulfite sequencing.
resultshASCs expressed endothelial cell markers including CD31, VEGF-R2, and VE-cadherin by combined treatment of VEGF and BMP4 under hypoxia condition. These differentiated cells exhibited the angiogenesis potential in vitro, and injection of these differentiated cells enhanced angiogenesis in the ischemic hindlimb of diabetic mice. Furthermore, it was found that hypoxia increased significantly EphrinB2 expression EC differentiation, which is greatly downregulated with EphrinB2 blockage. The methylation status in the proximal promoter CpG results showed that methylation of EphrinB2 promoter decreased in hASCs with exposure to hypoxia.
conclusionOur data demonstrate that hASCs can be efficiently induced to differentiate into vascular EC lineages which are mediated by demethylation of ephrinB2 under hypoxia condition.
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