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Stem Cell Reports. 2017 Dec 12;9(6):1754-1764. doi: 10.1016/j.stemcr.2017.10.023. Epub 2017 Nov 22.

Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells.

Author information

1
Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands; Department of Animal Biology, Faculty of Sciences, University of Málaga, Instituto Malagueño de Biomedicina (IBIMA), Campus de Teatinos s/n, 29071 Málaga, Spain; BIONAND, Centro Andaluz de Nanomedicina y Biotecnología (Junta de Andalucía, Universidad de Málaga), Severo Ochoa 35, 29590 Campanillas (Málaga), Spain.
2
Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
3
Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands; Department of Applied Stem Cell Technologies, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Building Zuidhorst, 7500 AE Enschede, the Netherlands.
4
Department of Animal Biology, Faculty of Sciences, University of Málaga, Instituto Malagueño de Biomedicina (IBIMA), Campus de Teatinos s/n, 29071 Málaga, Spain; BIONAND, Centro Andaluz de Nanomedicina y Biotecnología (Junta de Andalucía, Universidad de Málaga), Severo Ochoa 35, 29590 Campanillas (Málaga), Spain. Electronic address: jmperezp@uma.es.
5
Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands; Department of Applied Stem Cell Technologies, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Building Zuidhorst, 7500 AE Enschede, the Netherlands. Electronic address: robert.passier@utwente.nl.

Abstract

Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced) to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA) and bone morphogenetic protein 4 (BMP4) promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (pro)epicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (pro)epicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (pro)epicardial-like cells displaying functional properties (adhesion and spreading over the myocardium) of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (pro)epicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration.

KEYWORDS:

cardiovascular; differentiation; human pluripotent stem cells; proepicardium; progenitor cells

PMID:
29173898
PMCID:
PMC5785703
DOI:
10.1016/j.stemcr.2017.10.023
[Indexed for MEDLINE]
Free PMC Article

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