Differential Mechanisms of Myocardial Conduction Slowing by Adipose Tissue-Derived Stromal Cells Derived from Different Species.
Stem cell therapy is a promising therapeutic option to treat patients after myocardial infarction. However, the intramyocardial administration of large amounts of stem cells might generate a proarrhythmic substrate. Proarrhythmic effects can be explained by electrotonic and/or paracrine mechanisms. The narrow therapeutic time window for cell therapy and the presence of comorbidities limit the application of autologous cell therapy. The use of allogeneic or xenogeneic stem cells is a potential alternative to autologous cells, but differences in the proarrhythmic effects of adipose-derived stromal cells (ADSCs) across species are unknown. Using microelectrode arrays and microelectrode recordings, we obtained local unipolar electrograms and action potentials from monolayers of neonatal rat ventricular myocytes (NRVMs) that were cocultured with rat, human, or pig ADSCs (rADSCs, hADSCs, pADSCs, respectively). Monolayers of NRVMs were cultured in the respective conditioned medium to investigate paracrine effects. We observed significant conduction slowing in all cardiomyocyte cultures containing ADSCs, independent of species used (p < .01). All cocultures were depolarized compared with controls (p < .01). Only conditioned medium taken from cocultures with pADSCs and applied to NRVM monolayers demonstrated similar electrophysiological changes as the corresponding cocultures. We have shown that independent of species used, ADSCs cause conduction slowing in monolayers of NRVMs. In addition, pADSCs exert conduction slowing mainly by a paracrine effect, whereas the influence on conduction by hADSCs and rADSCs is preferentially by electrotonic interaction. Stem Cells Translational Medicine 2017;6:22-30.
Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Interuniversity Cardiology Institute of the Netherlands, Netherlands Heart Institute, Utrecht, The Netherlands.
Judith N
JN
Ten Sande
Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Interuniversity Cardiology Institute of the Netherlands, Netherlands Heart Institute, Utrecht, The Netherlands.
Nicoline W
NW
Smit
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands.
Mojtaba
M
Parvizi
Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Shirley C M
SC
van Amersfoorth
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands.
Josée A
JA
Plantinga
Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Pascal F H M
PF
van Dessel
Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Interuniversity Cardiology Institute of the Netherlands, Netherlands Heart Institute, Utrecht, The Netherlands.
Jacques M T
JM
de Bakker
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands.
Marco C
MC
Harmsen
Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|L'Institut de Rythmologie et de Modélisation Cardiaque, Université Bordeaux, Segalen, Bordeaux, France.
Ruben
R
Coronel
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D017208:Rats, Wistar; D013045:Species Specificity; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013552:Swine
D015820:Cadherins; D018031:Connexin 43; D017077:Culture Media, Conditioned
Adipose stromal cells; Cardiomyocytes; Conduction slowing; Electrophysiology; Paracrine