Functionality of Endothelial Cells and Pericytes From Human Pluripotent Stem Cells Demonstrated in Cultured Vascular Plexus and Zebrafish Xenografts

Orlova, Valeria V.; Drabsch, Yvette; Freund, Christian; Petrus‐Reurer, Sandra; Hil, Francijna E. van den; Muenthaisong, Suchitra; Dijke, Peter ten; Mummery, Christine L.

doi:10.1161/atvbaha.113.302598

Cited by 179 publications

(196 citation statements)

References 48 publications

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“…S3 A and B). EFNB2 and EPHB4 were the first identified and most widely used markers for AECs and VECs, respectively (6)(7)(8)(9)(10)(11)(12)(13)17). Specific targeting of the EFNB2 and EPHB4 locus was confirmed by junction PCR and Southern blot analysis (SI Appendix, Evaluation of Candidate Factors for Arteriovenous Specification.…”

Section: Significancementioning

confidence: 99%

“…Previous studies have shown progress in AEC differentiation (6)(7)(8)(9)(10)(11)(12)(13)(14), but the arterial-specific functions in vitro and the protection of ischemic tissue in vivo have not been well demonstrated in the resulting cells. Here, we use single-cell RNA sequencing (RNA-seq) of early mouse AECs and a CRISPR/Cas9-generated EFNB2-tdTomato/EPHB4-EGFP dual reporter human embryonic stem cell line to develop a protocol for differentiating human pluripotent stem cells into AECs using fully defined culture conditions.…”

mentioning

confidence: 99%

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Functional characterization of human pluripotent stem cell-derived arterial endothelial cells

Zhang

Chu

Hou

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

113

106

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Here, we report the derivation of arterial endothelial cells from human pluripotent stem cells that exhibit arterial-specific functions in vitro and in vivo. We combine single-cell RNA sequencing of embryonic mouse endothelial cells with an EFNB2-tdTomato/ EPHB4-EGFP dual reporter human embryonic stem cell line to identify factors that regulate arterial endothelial cell specification. The resulting xeno-free protocol produces cells with gene expression profiles, oxygen consumption rates, nitric oxide production levels, shear stress responses, and TNFα-induced leukocyte adhesion rates characteristic of arterial endothelial cells. Arterial endothelial cells were robustly generated from multiple human embryonic and induced pluripotent stem cell lines and have potential applications for both disease modeling and regenerative medicine.arterial endothelial cells | arterial-specific functions | myocardial infarction | single-cell RNA-seq | human pluripotent stem cell differentiation

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Section: Significancementioning

confidence: 99%

mentioning

confidence: 99%

Functional characterization of human pluripotent stem cell-derived arterial endothelial cells

Zhang

Chu

Hou

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

113

106

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“…with ECs in vitro demonstrate endothelial sprouting (Orlova et al, 2014a) (co-culture study). This has been demonstrated using pericytes derived from hiPSC and adventitial sorted cells from human saphenous vein digests (Campagnolo et al, 2010;Orlova et al, 2014a).…”

Section: Vascularisationmentioning

confidence: 99%

“…This has been demonstrated using pericytes derived from hiPSC and adventitial sorted cells from human saphenous vein digests (Campagnolo et al, 2010;Orlova et al, 2014a). Recapitulation of these phenomena in in vivo implantations would be highly advantageous.…”

Section: Vascularisationmentioning

confidence: 99%

“…As mentioned previously, Birbrair et al (Birbrair et al, 2013c) has demonstrated that Type 2 pericytes (nestin+/NG2+/CD146+) are myogenic, whilst their nestin-counterparts are not. Induced pericytes are also capable of myogenesis; in the presence of TGF-β and PDGF-BB, hiPSC-derived pericytes cocultured with hiPSC-derived ECs are capable of differentiation into contractile smooth muscle cells in vitro, as demonstrated by expression of the contractile markers SM22 and CNN1 (Orlova et al, 2014a). Moreover, CD105+ pericytes isolated from hiPSC-derived embryoid bodies have been found to aid in ischemic muscle recovery and display direct myogenic differentiation, as indicated by desmin expression, in addition to providing vascular support by integrating with the host vasculature (Dar et al, 2012).…”

Section: Skeletal Muscle and Cardiac Repairmentioning

confidence: 99%

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Pericytes, mesenchymal stem cells and their contributions to tissue repair

Wong

Rowley

Redpath

et al. 2015

Pharmacology & Therapeutics

152

110

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Regenerative medicine using mesenchymal stem cells for the purposes of tissue repair has garnered considerable public attention due to the potential of returning tissues and organs to a normal, healthy state after injury or damage has occurred. To achieve this, progenitor cells such as pericytes and bone marrow-derived mesenchymal stem cells can be delivered exogenously, mobilised and recruited from within the body or transplanted in the form organs and tissues grown in the laboratory from stem cells. In this review, we summarise the recent evidence supporting the use of endogenously mobilised stem cell populations to enhance tissue repair along with the use of mesenchymal stem cells and pericytes in the development of engineered tissues. Finally, we conclude with an overview of currently available therapeutic options to manipulate endogenous stem cells to promote tissue repair.

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A guide for blood–brain barrier models

Soliman,

Al‐khodor,

Yildirim Köken

et al. 2024

FEBS Letters

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Understanding the intricate mechanisms underlying brain‐related diseases hinges on unraveling the pivotal role of the blood–brain barrier (BBB), an essential dynamic interface crucial for maintaining brain equilibrium. This review offers a comprehensive analysis of BBB physiology, delving into its cellular and molecular components while exploring a wide range of in vivo and in vitro BBB models. Notably, recent advancements in 3D cell culture techniques are explicitly discussed, as they have significantly improved the fidelity of BBB modeling by enabling the replication of physiologically relevant environments under flow conditions. Special attention is given to the cellular aspects of in vitro BBB models, alongside discussions on advances in stem cell technologies, providing valuable insights into generating robust cellular systems for BBB modeling. The diverse array of cell types used in BBB modeling, depending on their sources, is meticulously examined in this comprehensive review, scrutinizing their respective derivation protocols and implications. By synthesizing diverse approaches, this review sheds light on the improvements of BBB models to capture physiological conditions, aiding in understanding BBB interactions in health and disease conditions to foster clinical developments.

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Functionality of Endothelial Cells and Pericytes From Human Pluripotent Stem Cells Demonstrated in Cultured Vascular Plexus and Zebrafish Xenografts

Abstract: Objective-Endothelial cells (ECs), pericytes, and vascular smooth muscle cells (vSMCs)

Cited by 179 publications

References 48 publications

Functional characterization of human pluripotent stem cell-derived arterial endothelial cells

Functional characterization of human pluripotent stem cell-derived arterial endothelial cells

Pericytes, mesenchymal stem cells and their contributions to tissue repair

A guide for blood–brain barrier models

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