title: Fibroblasts support functional integration of purified embryonic stem cell-derived cardiomyocytes into avital myocardial tissue.
abstract: Transplantation of purified pluripotent stem cell-derived cardiomyocytes into damaged myocardium might become a therapy to improve contractile function after myocardial infarction. However, engraftment remains problematic. Aim of this study was to investigate whether murine embryonic fibroblasts (MEFs) support the functional integration of purified embryonic stem cell-derived cardiomyocytes (ES-CMs). Neonatal murine ventricular tissue slices were subjected to oxygen and glucose deprivation to simulate irreversible ischemia. Vital tissue slices served as control. Vital and avital tissue slices were cultured with or without MEFs before coculturing with clusters of puromycin-selected ES-CMs. Integration of ES-CM clusters was assessed morphologically, motility by long-term microscopy, and functional integration by isometric force measurements. We observed a good morphological integration into vital but a poor integration into avital slices. Adding MEFs improved morphological integration into irreversibly damaged slices and enabled purified ES-CMs to migrate and to confer force. We conclude that noncardiomyocytes like MEFs support morphological integration and force transmission of purified ES-CMs by enabling adhesion and migration.
authors.affiliation: Institute for Neurophysiology, University of Cologne, Cologne, Germany.
authors.forename: Jiaoya
authors.initials: J
authors.lastname: Xi
authors.forename: Markus
authors.initials: M
authors.lastname: Khalil
authors.forename: Dimitry
authors.initials: D
authors.lastname: Spitkovsky
authors.forename: Tobias
authors.initials: T
authors.lastname: Hannes
authors.forename: Kurt
authors.initials: K
authors.lastname: Pfannkuche
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Tomo
authors.initials: T
authors.lastname: Sarić
authors.forename: Konrad
authors.initials: K
authors.lastname: Brockmeier
authors.forename: Juergen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Frank
authors.initials: F
authors.lastname: Pillekamp
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D018920:Coculture Techniques / Q000379:methods; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology*; D006352:Heart Ventricles / Q000473:pathology*; D051379:Mice; D008867:Microtomy; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D044968:Regenerative Medicine; D023822:Tissue Engineering / Q000379:methods*