title: Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter Activity.
abstract: 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.
authors.affiliation: Laboratory of Biology, Medical School, University of Ioannina, Ioannina, Greece; Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece.
authors.forename: Violetta A
authors.initials: VA
authors.lastname: Maltabe
authors.affiliation: Ceramics and Composites Laboratory Department of Materials Science and Engineering, University of Ioannina, Ioannina, Greece.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Barka
authors.affiliation: Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece; Cardiovascular Research Institute, Ioannina, Greece.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Kontonika
authors.affiliation: Laboratory of Biology, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Florou
authors.affiliation: Laboratory of Biology, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Kouvara-Pritsouli
authors.affiliation: Ceramics and Composites Laboratory Department of Materials Science and Engineering, University of Ioannina, Ioannina, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Roumpi
authors.affiliation: Ceramics and Composites Laboratory Department of Materials Science and Engineering, University of Ioannina, Ioannina, Greece.
authors.forename: Simeon
authors.initials: S
authors.lastname: Agathopoulos
authors.affiliation: Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece; Cardiovascular Research Institute, Ioannina, Greece.
authors.forename: Theofilos M
authors.initials: TM
authors.lastname: Kolettis
authors.affiliation: Laboratory of Biology, Medical School, University of Ioannina, Ioannina, Greece; Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece.
authors.forename: Panos
authors.identifier: 0000-0003-0378-5619
authors.initials: P
authors.lastname: Kouklis