Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter Activity

Embryonic Stem (ES) or induced Pluripotent Stem (iPS) cells are important sources for cardiomyocyte generation, targeted for regenerative therapies. Several in vitro protocols are currently utilized for their differentiation, but the value of cell-based approaches remains unclear. Here, we character...

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Main Authors: Violetta A. Maltabe, Eleonora Barka, Marianthi Kontonika, Dimitra Florou, Maria Kouvara-Pritsouli, Maria Roumpi, Simeon Agathopoulos, Theofilos M. Kolettis, Panos Kouklis
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/8305624
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author Violetta A. Maltabe
Eleonora Barka
Marianthi Kontonika
Dimitra Florou
Maria Kouvara-Pritsouli
Maria Roumpi
Simeon Agathopoulos
Theofilos M. Kolettis
Panos Kouklis
author_facet Violetta A. Maltabe
Eleonora Barka
Marianthi Kontonika
Dimitra Florou
Maria Kouvara-Pritsouli
Maria Roumpi
Simeon Agathopoulos
Theofilos M. Kolettis
Panos Kouklis
author_sort Violetta A. Maltabe
collection DOAJ
description Embryonic Stem (ES) or induced Pluripotent Stem (iPS) cells are important sources for cardiomyocyte generation, targeted for regenerative therapies. Several in vitro protocols are currently utilized for their differentiation, but the value of cell-based approaches remains unclear. Here, we characterized a cardiovascular progenitor population derived during ES differentiation, after selection based on VE-cadherin promoter (Pvec) activity. ESCs were genetically modified with an episomal vector, allowing the expression of puromycin resistance gene, under Pvec activity. Puromycin-surviving cells displayed cardiac and endothelial progenitor cells characteristics. Expansion and self-renewal of this cardiac and endothelial dual-progenitor population (CEDP) were achieved by Wnt/β-catenin pathway activation. CEDPs express early cardiac developmental stage-specific markers but not markers of differentiated cardiomyocytes. Similarly, CEDPs express endothelial markers. However, CEDPs can undergo differentiation predominantly to cTnT+ (~47%) and VE-cadherin+ (~28%) cells. Transplantation of CEDPs in the left heart ventricle of adult rats showed that CEDPs-derived cells survive and differentiate in vivo for at least 14 days after transplantation. A novel, dual-progenitor population was isolated during ESCs differentiation, based on Pvec activity. This lineage can self-renew, permitting its maintenance as a source of cardiovascular progenitor cells and constitutes a useful source for regenerative approaches.
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spelling doaj-art-c4dfa044939b406f9f9e615afaf7482c2025-08-20T02:18:47ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/83056248305624Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter ActivityVioletta A. Maltabe0Eleonora Barka1Marianthi Kontonika2Dimitra Florou3Maria Kouvara-Pritsouli4Maria Roumpi5Simeon Agathopoulos6Theofilos M. Kolettis7Panos Kouklis8Laboratory of Biology, Medical School, University of Ioannina, Ioannina, GreeceCeramics and Composites Laboratory Department of Materials Science and Engineering, University of Ioannina, Ioannina, GreeceDepartment of Cardiology, University of Ioannina Medical School, Ioannina, GreeceLaboratory of Biology, Medical School, University of Ioannina, Ioannina, GreeceLaboratory of Biology, Medical School, University of Ioannina, Ioannina, GreeceCeramics and Composites Laboratory Department of Materials Science and Engineering, University of Ioannina, Ioannina, GreeceCeramics and Composites Laboratory Department of Materials Science and Engineering, University of Ioannina, Ioannina, GreeceDepartment of Cardiology, University of Ioannina Medical School, Ioannina, GreeceLaboratory of Biology, Medical School, University of Ioannina, Ioannina, GreeceEmbryonic Stem (ES) or induced Pluripotent Stem (iPS) cells are important sources for cardiomyocyte generation, targeted for regenerative therapies. Several in vitro protocols are currently utilized for their differentiation, but the value of cell-based approaches remains unclear. Here, we characterized a cardiovascular progenitor population derived during ES differentiation, after selection based on VE-cadherin promoter (Pvec) activity. ESCs were genetically modified with an episomal vector, allowing the expression of puromycin resistance gene, under Pvec activity. Puromycin-surviving cells displayed cardiac and endothelial progenitor cells characteristics. Expansion and self-renewal of this cardiac and endothelial dual-progenitor population (CEDP) were achieved by Wnt/β-catenin pathway activation. CEDPs express early cardiac developmental stage-specific markers but not markers of differentiated cardiomyocytes. Similarly, CEDPs express endothelial markers. However, CEDPs can undergo differentiation predominantly to cTnT+ (~47%) and VE-cadherin+ (~28%) cells. Transplantation of CEDPs in the left heart ventricle of adult rats showed that CEDPs-derived cells survive and differentiate in vivo for at least 14 days after transplantation. A novel, dual-progenitor population was isolated during ESCs differentiation, based on Pvec activity. This lineage can self-renew, permitting its maintenance as a source of cardiovascular progenitor cells and constitutes a useful source for regenerative approaches.http://dx.doi.org/10.1155/2016/8305624
spellingShingle Violetta A. Maltabe
Eleonora Barka
Marianthi Kontonika
Dimitra Florou
Maria Kouvara-Pritsouli
Maria Roumpi
Simeon Agathopoulos
Theofilos M. Kolettis
Panos Kouklis
Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter Activity
Stem Cells International
title Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter Activity
title_full Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter Activity
title_fullStr Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter Activity
title_full_unstemmed Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter Activity
title_short Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter Activity
title_sort isolation of an es derived cardiovascular multipotent cell population based on ve cadherin promoter activity
url http://dx.doi.org/10.1155/2016/8305624
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