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

Marta Vilà-González; Sophia Kelaini; Corey Magee; Rachel Caines; David Campbell; Magdalini Eleftheriadou; Amy Cochrane; Daiana Drehmer; Marianna Tsifaki; Karla O'Neill; Edoardo Pedrini; Chunbo Yang; Reinhold Medina; Denise McDonald; David Simpson; Anna Zampetaki; Lingfang Zeng; David Grieve; Noemi Lois; Alan W Stitt; Andriana Margariti

doi:10.1002/stem.2936

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

Marta Vilà-González, Sophia Kelaini, Corey Magee, Rachel Caines, David Campbell, Magdalini Eleftheriadou, Amy Cochrane, Daiana Drehmer, Marianna Tsifaki, Karla O'Neill, Edoardo Pedrini, Chunbo Yang, Reinhold Medina, Denise McDonald, David Simpson, Anna Zampetaki, Lingfang Zeng, David Grieve, Noemi Lois, Alan W StittAndriana Margariti^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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Abstract

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. Stem Cells 2018.

Original language	English
Pages (from-to)	226
Journal	Stem Cells
Volume	37
Issue number	2
Early online date	29 Oct 2018
DOIs	https://doi.org/10.1002/stem.2936
Publication status	Published - 17 Nov 2018
Externally published	Yes

Bibliographical note

Keywords

Endothelial cells
ESM1
Induced pluripotent stem cells
Reprogramming
Vascular disease

ASJC Scopus subject areas

Molecular Medicine
Developmental Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/stem.2936Licence: CC BY

Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells through ESM1 Signalling
Copyright 2018 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 1.51 MBLicence: CC BY

Cite this

Vilà-González, M., Kelaini, S., Magee, C., Caines, R., Campbell, D., Eleftheriadou, M., Cochrane, A., Drehmer, D., Tsifaki, M., O'Neill, K., Pedrini, E., Yang, C., Medina, R., McDonald, D., Simpson, D., Zampetaki, A., Zeng, L., Grieve, D., Lois, N., ... Margariti, A. (2018). Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling. Stem Cells, 37(2), 226. https://doi.org/10.1002/stem.2936

Vilà-González, Marta ; Kelaini, Sophia ; Magee, Corey ; Caines, Rachel ; Campbell, David ; Eleftheriadou, Magdalini ; Cochrane, Amy ; Drehmer, Daiana ; Tsifaki, Marianna ; O'Neill, Karla ; Pedrini, Edoardo ; Yang, Chunbo ; Medina, Reinhold ; McDonald, Denise ; Simpson, David ; Zampetaki, Anna ; Zeng, Lingfang ; Grieve, David ; Lois, Noemi ; Stitt, Alan W ; Margariti, Andriana. / Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling. In: Stem Cells. 2018 ; Vol. 37, No. 2. pp. 226.

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title = "Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling",

abstract = "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. Stem Cells 2018.",

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Vilà-González, M, Kelaini, S, Magee, C, Caines, R, Campbell, D, Eleftheriadou, M, Cochrane, A, Drehmer, D, Tsifaki, M, O'Neill, K, Pedrini, E, Yang, C, Medina, R , McDonald, D , Simpson, D, Zampetaki, A, Zeng, L, Grieve, D , Lois, N , Stitt, AW & Margariti, A 2018, 'Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling', Stem Cells, vol. 37, no. 2, pp. 226. https://doi.org/10.1002/stem.2936

Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling. / Vilà-González, Marta; Kelaini, Sophia; Magee, Corey; Caines, Rachel; Campbell, David; Eleftheriadou, Magdalini; Cochrane, Amy; Drehmer, Daiana; Tsifaki, Marianna; O'Neill, Karla; Pedrini, Edoardo; Yang, Chunbo; Medina, Reinhold ; McDonald, Denise ; Simpson, David; Zampetaki, Anna; Zeng, Lingfang; Grieve, David ; Lois, Noemi ; Stitt, Alan W ; Margariti, Andriana.

In: Stem Cells, Vol. 37, No. 2, 17.11.2018, p. 226.

Research output: Contribution to journal › Article › peer-review

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AU - Vilà-González, Marta

AU - Kelaini, Sophia

AU - Magee, Corey

AU - Caines, Rachel

AU - Campbell, David

AU - Eleftheriadou, Magdalini

AU - Cochrane, Amy

AU - Drehmer, Daiana

AU - Tsifaki, Marianna

AU - O'Neill, Karla

AU - Pedrini, Edoardo

AU - Yang, Chunbo

AU - Medina, Reinhold

AU - McDonald, Denise

AU - Simpson, David

AU - Zampetaki, Anna

AU - Zeng, Lingfang

AU - Grieve, David

AU - Lois, Noemi

AU - Stitt, Alan W

AU - Margariti, Andriana

PY - 2018/11/17

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N2 - 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. Stem Cells 2018.

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KW - Induced pluripotent stem cells

KW - Reprogramming

KW - Vascular disease

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

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Elucidating the underlying mechanisms of diabetic endotheliopathy using patient specific induced pluripotent stem cells

Andriana Margariti

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Student theses

Elucidating the underlying mechanisms of diabetic endotheliopathy using patient specific induced pluripotent stem cells

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Andriana Margariti

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