ArticlePloS one2016
Multifactorial Optimizations for Directing Endothelial Fate from Stem Cells.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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
11 citing papers in PubMed, 21 citations in OpenAlex.
- Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026Review
- An Endothelial Cell Is Not Simply an Endothelial Cell.Stem cells and development · 2024Review
- Migration and proliferation drive the emergence of patterns in co-cultures of differentiating vascular progenitor cells.Mathematical biosciences and engineering : MBE · 2024Article
- Evaluation of Antibodies for Vascular Smooth Muscle Cell Characterization.Stem cell and regenerative medicine (Wilmington, Del.) · 2024Article
- Mouse embryonic stem cell-derived blood-brain barrier model: applicability to studying antibody triggered receptor mediated transcytosis.Fluids and barriers of the CNS · 2023Article
- Slow diffusion on the monolayer culture enhances auto/paracrine effects of Noggin in differentiation of human iPS cells induced by BMP.Biochemistry and biophysics reports · 2022Article
- Article
- VEGF secreted by mesenchymal stem cells mediates the differentiation of endothelial progenitor cells into endothelial cells via paracrine mechanisms.Molecular medicine reports · 2018Article
- Combinatorial Extracellular Matrix Microenvironments for Probing Endothelial Differentiation of Human Pluripotent Stem Cells.Scientific reports · 2017Article
- A Network Model to Explore the Effect of the Micro-environment on Endothelial Cell Behavior during Angiogenesis.Frontiers in physiology · 2017Article
- Climbing the mountain: experimental design for the efficient optimization of stem cell bioprocessing.Journal of biological engineering · 2017Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Embryonic stem cells (ESC) and induced pluripotent stem (iPS) cells are attractive in vitro models of vascular development, therapeutic angiogenesis, and tissue engineering. However, distinct ESC and iPS cell lines respond differentially to the same microenvironmental factors. Developing improved/optimized differentiation methodologies tailored/applicable in a number of distinct iPS and ESC lines remains a challenge in the field. Currently published methods for deriving endothelial cells (EC) robustly generate high numbers of endothlelial progenitor cells (EPC) within a week, but their maturation to definitive EC is much more difficult, taking up to 2 months and requiring additional purification. Therefore, we set out to examine combinations/levels of putative EC induction factors-utilizing our stage-specific chemically-defined derivation methodology in 4 ESC lines including: kinetics, cell seeding density, matrix signaling, as well as medium treatment with vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). The results indicate that temporal development in both early and late stages is the most significant factor generating the desired cells. The generation of early Flk-1+/KDR+ vascular progenitor cells (VPC) from pluripotent ESC is directed predominantly by high cell seeding density and matrix signaling from fibronectin, while VEGF supplementation was NOT statistically significant in more than one cell line, especially with fibronectin matrix which sequesters autocrine VEGF production by the differentiating stem cells. Although some groups have shown that the GSK3-kinase inhibitor (CHIR) can facilitate EPC fate, it hindered the generation of KDR+ cells in our preoptimized medium formulations. The methods summarized here significantly increased the production of mature vascular endothelial (VE)-cadherin+ EC, with up to 93% and 57% purity from mouse and human ESC, respectively, before VE-cadherin+ EC purification.
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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.