ArticleStem cell research & therapy2018
Role of Notch1 in the arterial specification and angiogenic potential of mouse embryonic stem cell-derived endothelial cells.
Article in Stem cell research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 27 citations in OpenAlex.
- Comparative evaluation of cell types for endothelialization in cardiovascular tissue engineering.Iranian journal of basic medical sciences · 2026Review
- A novel NOTCH1 nonsense variant in a bicuspid aortic valve family with intrafamilial clinical heterogeneity.BMC cardiovascular disorders · 2025Article
- Optimizing extracellular matrix for endothelial differentiation using a design of experiments approach.Scientific reports · 2025Article
- Bioengineering Cell Therapy for Treatment of Peripheral Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Impaired Angiogenic Function of Fetal Endothelial Progenitor Cells viaInternational journal of molecular sciences · 2023Article
- Laminin 411 mediates endothelial specification via multiple signaling axes that converge on β-catenin.Stem cell reports · 2022Article
- Effects of limonin treatment on the survival of random skin flaps in mice.Frontiers in surgery · 2022Article
- Notch2 suppression mimicking changes in human pulmonary hypertension modulates Notch1 and promotes endothelial cell proliferation.American journal of physiology. Heart and circulatory physiology · 2021Article
- Selection of different endothelialization modes and different seed cells for tissue-engineered vascular graft.Bioactive materials · 2021Review
- Hypoimmune induced pluripotent stem cell-derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Adipose matrix complex: a high-rigidity collagen-rich adipose-derived material for fat grafting.Aging · 2021Article
- Single-cell transcriptomic profiling and characterization of endothelial progenitor cells: new approach for finding novel markers.Stem cell research & therapy · 2021Article
- Interactions Among Nerve Regeneration, Angiogenesis, and the Immune Response Immediately After Sciatic Nerve Crush Injury in Sprague-Dawley Rats.Frontiers in cellular neuroscience · 2021Article
- COUP-TFII in Health and Disease.Cells · 2019Review
- Arsenic Trioxide Suppresses Tumor Growth through Antiangiogenesis via Notch Signaling Blockade in Small-Cell Lung Cancer.BioMed research international · 2019Article
- Therapeutic potential of pravastatin for random skin flaps necrosis: involvement of promoting angiogenesis and inhibiting apoptosis and oxidative stress.Drug design, development and therapy · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundEndothelial cells have been shown to mediate angiogenesis in ischemic injury sites and contribute to the repair of damaged tissues. However, the treatment of ischemic disease requires a significant number of endothelial cells, which are difficult to isolate from patients. Embryonic stem cells have been considered a potential source of therapeutic cells due to their unlimited self-renewal and pluripotent properties. With regard to vascular development, Notch1 has been established as a key regulator of the specification of arterial endothelial cells.
methodsUsing a doxycycline-induced expression system of the intracellular domain of Notch1, we explored the role of Notch1 in the differentiation of embryonic stem cells to arterial endothelial cells. The therapeutic effect of the arterial endothelial cells was investigated in a murine hindlimb ischemia model. The blood perfusion rate in the ischemic limb was determined by laser Doppler perfusion imaging, and vasculogenesis was quantified using immunocytochemistry.
resultsInduced expression of the intracellular domain of Notch1 increased the levels of endothelial markers, such as CD31 and VE-cadherin, in differentiated endothelial cells. Induction of intracellular domain of Notch1 stimulated expression of the arterial-type endothelial cell markers (Nrp1 and Ephrin B2), but not the venous-type endothelial cell markers (Nrp2 and Coup-TFII). In addition, overexpression of intracellular domain of Notch1 resulted in increased expression of CXCR4, a chemokine receptor involved in vascular development. Induction of intracellular domain of Notch1 increased endothelial tube formation and migration of differentiated endothelial cells. Intramuscular administration of Notch1-induced arterial endothelial cells was more effective than administration of the control endothelial cells in restoring the blood flow in an ischemic hindlimb mouse model. Transplantation of Notch1-induced arterial endothelial cells augmented the number of blood vessels and incorporation of endothelial cells into newly formed blood vessels.
conclusionsThese results suggest that Notch1 promotes endothelial maturation and arterial specification during the differentiation of embryonic stem cells to endothelial cells and increases the angiogenic potential of endothelial cells.
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