Reprogrammed Human Endothelial Cells

Cheng, Zhongjian; Verma, Suresh; Losordo, Douglas W.; Kishore, Raj

doi:10.1161/circresaha.117.310573

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…It is, thus, imperative that we expand our understanding and, thus, identify more key factors that may facilitate faster and safer EC generation. In addition, differentiated ECs can shift their phenotype away from the endothelial lineage after prolonged cell culture and exhibit an immature phenotype with previous efforts focusing on preservation of EC stability and commitment . Such observations of EC instability were also made in our study, in which ESM1 levels were reduced with increasing passages (after 15 passages; Supporting Information Fig.…”

Section: Discussionsupporting

confidence: 85%

“…Even though there are many approaches in reprogramming methodology , many of the iPS cell generation mechanisms and their subsequent differentiation toward various cell lineages still remain relatively unclear. Moreover, prolonged culture of iPS‐ECs populations can limit their clinical application and since they are not derived from intact blood vessels, they show an immature phenotype . iPS‐ECs generation efficiency has increased over the last years, resulting in nearly pure populations of endothelial‐like cells .…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling

et al. 2018

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The mortality rate for (cardio)‐vascular disease is one of the highest in the world, so a healthy functional endothelium is of outmost importance against vascular disease. In this study, human induced pluripotent stem (iPS) cells were reprogrammed from 1 ml blood of healthy donors and subsequently differentiated into endothelial cells (iPS‐ECs) with typical EC characteristics. This research combined iPS cell technologies and next‐generation sequencing to acquire an insight into the transcriptional regulation of iPS‐ECs. We identified endothelial cell‐specific molecule 1 (ESM1) as one of the highest expressed genes during EC differentiation, playing a key role in EC enrichment and function by regulating connexin 40 (CX40) and eNOS. Importantly, ESM1 enhanced the iPS‐ECs potential to improve angiogenesis and neovascularisation in in vivo models of angiogenesis and hind limb ischemia. These findings demonstrated for the first time that enriched functional ECs are derived through cell reprogramming and ESM1 signaling, opening the horizon for drug screening and cell‐based therapies for vascular diseases. Therefore, this study showcases a new approach for enriching and enhancing the function of induced pluripotent stem (iPS) cell‐derived ECs from a very small amount of blood through ESM1 signaling, which greatly enhances their functionality and increases their therapeutic potential. S tem C ells 2019;37:226–239

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling

et al. 2018

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Comparative Analysis of Blood‐Derived Endothelial Cells for Designing Next‐Generation Personalized Organ‐on‐Chips

Mathur

Tronolone

Jain

2021

JAHA

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Background Organ‐on‐chip technology has accelerated in vitro preclinical research of the vascular system, and a key strength of this platform is its promise to impact personalized medicine by providing a primary human cell–culture environment where endothelial cells are directly biopsied from individual tissue or differentiated through stem cell biotechniques. However, these methods are difficult to adopt in laboratories, and often result in impurity and heterogeneity of cells. This limits the power of organ‐chips in making accurate physiological predictions. In this study, we report the use of blood‐derived endothelial cells as alternatives to primary and induced pluripotent stem cell–derived endothelial cells. Methods and Results Here, the genotype, phenotype, and organ‐chip functional characteristics of blood‐derived outgrowth endothelial cells were compared against commercially available and most used primary endothelial cells and induced pluripotent stem cell–derived endothelial cells. The methods include RNA‐sequencing, as well as criterion standard assays of cell marker expression, growth kinetics, migration potential, and vasculogenesis. Finally, thromboinflammatory responses under shear using vessel‐chips engineered with blood‐derived endothelial cells were assessed. Blood‐derived endothelial cells exhibit the criterion standard hallmarks of typical endothelial cells. There are differences in gene expression profiles between different sources of endothelial cells, but blood‐derived cells are relatively closer to primary cells than induced pluripotent stem cell–derived. Furthermore, blood‐derived endothelial cells are much easier to obtain from individuals and yet, they serve as an equally effective cell source for functional studies and organ‐chips compared with primary cells or induced pluripotent stem cell–derived cells. Conclusions Blood‐derived endothelial cells may be used in preclinical research for developing more robust and personalized next‐generation disease models using organ‐on‐chips.

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Reprogrammed Human Endothelial Cells

Cited by 2 publications

References 17 publications

Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling

Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling

Comparative Analysis of Blood‐Derived Endothelial Cells for Designing Next‐Generation Personalized Organ‐on‐Chips

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