title: The Derivation of Primary Human Epicardium-Derived Cells.
abstract: To develop therapeutic strategies for the regeneration of lost heart muscle after myocardial infarction (MI), a source of functional new muscle cells and associated coronary vessels must be identified. The epicardium is a source of several cardiovascular cell types during heart development and is widely regarded as a resident progenitor population, which becomes dormant during adulthood. In adult mice, MI induces epicardial reactivation characterized by an upregulation of fetal genes and subsequent epicardium derived cell (EPDC) proliferation, migration, and differentiation. Determining whether the epicardium can be therapeutically targeted following cardiovascular disease requires an in vitro system for the study of adult human EPDCs (hEPDCs). This protocol describes techniques to establish and maintain human epicardium explant cultures from patient-derived right atrial appendage biopsies and documents methods to probe the resultant outgrowth of hEPDCs. The model facilitates a high-throughput approach to either genetic or chemical phenotypic screening for drug-like modifiers of hEPDC activation and potential cell fate.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.|Department of Chemistry, Chemistry Research Laboratory, Oxford, United Kingdom.|These authors contributed equally to this study.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Clunie-O'Connor
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands.|These authors contributed equally to this study.
authors.forename: Anke M
authors.initials: AM
authors.lastname: Smits
authors.affiliation: Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Antoniades
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, Oxford, United Kingdom.|Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Russell
authors.affiliation: The Hatter Cardiovascular Institute, University College, London, United Kingdom.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Yellon
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Goumans
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Riley
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology; D010496:Pericardium / Q000166:cytology* / Q000473:pathology; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta
keywords: epicardium; hEPDCs; heart; human; regeneration