ArticleStem cell research & therapy2015
Efficient differentiation of human embryonic stem cells to arterial and venous endothelial cells under feeder- and serum-free conditions.
Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- Protocol for PI3K inhibitor-free differentiation and maturation of human iPSC-derived arterial- and venous-like endothelial cells.STAR protocols · 2026Article
- Inferring cell-specific gene regulatory networks based on causal graph embedding.Cell reports methods · 2026Article
- Feeder-Free Generation of Lymphatic Endothelial Cells from Human Induced Pluripotent Stem Cells.bioRxiv : the preprint server for biology · 2026Article
- iPSC-Derived Endothelial Cells as Experimental Models for Predictive and Personalized Strategies in Cardiovascular and Cerebrovascular Disease.International journal of molecular sciences · 2026Review
- Efficient generation of liver sinusoidal endothelial-like cells secreting coagulation factor VIII from human induced pluripotent stem cells.Molecular therapy. Methods & clinical development · 2024Article
- An Endothelial Cell Is Not Simply an Endothelial Cell.Stem cells and development · 2024Review
- Building a human lung from pluripotent stem cells to model respiratory viral infections.Respiratory research · 2024Review
- Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells.Circulation · 2024Article
- Bioprinted vascular tissue: Assessing functions from cellular, tissue to organ levels.Materials today. Bio · 2023Review
- Transcription factors and splice factors - interconnected regulators of stem cell differentiation.Current stem cell reports · 2023Article
- The critical role of neutrophil-endothelial cell interactions in sepsis: new synergistic approaches employing organ-on-chip, omics, immune cell phenotyping andFrontiers in cellular and infection microbiology · 2023Review
- Extracellular matrix cues regulate the differentiation of pluripotent stem cell-derived endothelial cells.Frontiers in cardiovascular medicine · 2023Review
- Comprehensive Review of the Vascular Niche in Regulating Organ Regeneration and Fibrosis.Stem cells translational medicine · 2022Review
- The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V.International journal of molecular sciences · 2022Review
- Article
- High-efficient serum-free differentiation of endothelial cells from human iPS cells.Stem cell research & therapy · 2022Article
- Role of TGFβ1 and WNT6 in FGF2 and BMP4-driven endothelial differentiation of murine embryonic stem cells.Angiogenesis · 2022Article
- Establishment of an in vitro safety assessment model for lipid-lowering drugs using same-origin human pluripotent stem cell-derived cardiomyocytes and endothelial cells.Acta pharmacologica Sinica · 2022Article
- A three-dimensional culture system for generating cardiac spheroids composed of cardiomyocytes, endothelial cells, smooth-muscle cells, and cardiac fibroblasts derived from human induced-pluripotent stem cells.Frontiers in bioengineering and biotechnology · 2022Article
- Review
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5 authors.
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Abstract
backgroundHeterogeneity of endothelial cells (ECs) is a hallmark of the vascular system which may impact the development and management of vascular disorders. Despite the tremendous progress in differentiation of human embryonic stem cells (hESCs) towards endothelial lineage, differentiation into arterial and venous endothelial phenotypes remains elusive. Additionally, current differentiation strategies are hampered by inefficiency, lack of reproducibility, and use of animal-derived products.
methodsTo direct the differentiation of hESCs to endothelial subtypes, H1- and H9-hESCs were seeded on human plasma fibronectin and differentiated under chemically defined conditions by sequential modulation of glycogen synthase kinase-3 (GSK-3), basic fibroblast growth factor (bFGF), bone morphogenetic protein 4 (BMP4) and vascular endothelial growth factor (VEGF) signaling pathways for 5 days. Following the initial differentiation, the endothelial progenitor cells (CD34(+)CD31(+) cells) were sorted and terminally differentiated under serum-free conditions to arterial and venous ECs. The transcriptome and secretome profiles of the two distinct populations of hESC-derived arterial and venous ECs were characterized. Furthermore, the safety and functionality of these cells upon in vivo transplantation were characterized.
resultsSequential modulation of hESCs with GSK-3 inhibitor, bFGF, BMP4 and VEGF resulted in stages reminiscent of primitive streak, early mesoderm/lateral plate mesoderm, and endothelial progenitors under feeder- and serum-free conditions. Furthermore, these endothelial progenitors demonstrated differentiation potential to almost pure populations of arterial and venous endothelial phenotypes under serum-free conditions. Specifically, the endothelial progenitors differentiated to venous ECs in the absence of VEGF, and to arterial phenotype under low concentrations of VEGF. Additionally, these hESC-derived arterial and venous ECs showed distinct molecular and functional profiles in vitro. Furthermore, these hESC-derived arterial and venous ECs were nontumorigenic and were functional in terms of forming perfused microvascular channels upon subcutaneous implantation in the mouse.
conclusionsWe report a simple, rapid, and efficient protocol for directed differentiation of hESCs into endothelial progenitor cells capable of differentiation to arterial and venous ECs under feeder-free and serum-free conditions. This could offer a human platform to study arterial-venous specification for various applications related to drug discovery, disease modeling and regenerative medicine in the future.
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