title: Physiological differences between transplanted and host tissue cause functional decoupling after in vitro transplantation of human embryonic stem cell-derived cardiomyocytes.
abstract: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) might provide cells to repopulate injured myocardium. Electrical coupling of these cells to the host myocardium is a prerequisite for improved functionality. The aim of this study was to investigate electrical interaction of hESC-CMs with myocardial tissue and to identify factors challenging functional integration. Beating clusters containing hESC-CMs were cocultured in vitro with viable slices of late-stage embryonic murine ventricles. Field potentials recorded with micro-electrode arrays and video data were analyzed. The effects of heptanol, electrical pacing, beta-adrenergic, and muscarinic stimulation on coupling were studied. Beating clusters integrated morphologically and functionally resulting in a synchronized beating pattern after two to four days of coculture. Heptanol-induced conduction block between transplanted cells and host tissue and immunoreactivity for connexin43 suggested electrical coupling via gap junctions. Beta-adrenergic or muscarinic stimulation induced uncoupling and arrhythmias probably due to genetically determined differences of hormonal modulation of spontaneous beating rates of transplanted cells and host tissue. HESC-CMs can integrate functionally and develop synchronized beating. Interventions unraveling the different electrophysiological properties of transplanted and host tissue induce functional disintegration. Successful cellular replacement has to improve coupling but should also aim to transplant cardiomyocytes with similar electrophysiological properties as the host tissue.
authors.affiliation: Pediatric Cardiology, University of Cologne, Cologne, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Pillekamp
authors.forename: Marcel
authors.initials: M
authors.lastname: Halbach
authors.forename: Michael
authors.initials: M
authors.lastname: Reppel
authors.forename: Kurt
authors.initials: K
authors.lastname: Pfannkuche
authors.forename: Rewa
authors.initials: R
authors.lastname: Nazzal
authors.forename: Filomain
authors.initials: F
authors.lastname: Nguemo
authors.forename: Matthias
authors.initials: M
authors.lastname: Matzkies
authors.forename: Olga
authors.initials: O
authors.lastname: Rubenchyk
authors.forename: Tobias
authors.initials: T
authors.lastname: Hannes
authors.forename: Markus
authors.initials: M
authors.lastname: Khalil
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Narayanswami
authors.initials: N
authors.lastname: Sreeram
authors.forename: Konrad
authors.initials: K
authors.lastname: Brockmeier
authors.forename: Juergen
authors.initials: J
authors.lastname: Hescheler
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004594:Electrophysiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D017629:Gap Junctions / Q000378:metabolism; D006329:Heart Conduction System / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D046529:Microscopy, Electron, Transmission; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation* / Q000648:ultrastructure
chemical_list: D000318:Adrenergic beta-Agonists