Abstract 14805: Engraftment Characteristics of Human Adult Mesenchymal Stem Cells Expose Electronic and Paracrine Pro-Arrhythmic Mechanisms in Myocardial Cultures
Background: After transplantation into myocardium, mesenchymal stem cells (MSCs) may engraft and exert their effects on cardiac function. However, engraftment in vivo is difficult to be controlled and therefore tailored assessment of potential adverse effects is hampered. This study investigates the role of engraftment characteristics of MSC (e.g. different numbers and distribution patterns) on arrhythmicity in controlled in vitro models.
Methods & Results: Co-cultures of adult human (h) MSCs (7%/28%) with neonatal rat cardiomyocytes (nrCMCs) were prepared in diffuse or clustered distribution patterns. Electrophysiological effects were studied by optical-mapping and patch-clamp at day 9. In diffuse co-cultures, hMSCs quantity-dependently decreased nrCMC excitability, slowed conduction, prolonged APD90 and increased APD dispersion. Triggered activity (12%,n=66 vs 0%,n=39 in controls) and increased inducibility of reentry (53%,n=15 vs 6%,n=16 in controls) were observed in 28% hMSC co-cultures. MSC-clusters increased APD90 and slowed conduction locally, and increased reentry-inducibility (23%,n=30), while no triggered activity was observed. Pharmacological heterocellular electrical uncoupling increased excitability and conduction velocity by 139% in co-cultures, but did not alter APD90. Transwell experiments showed that hMSCs quantity-dependently increased APD90, APD dispersion and inducibility of reentry, while conduction velocity was unaltered. Molecular studies showed differences in ion channel mRNA levels.
Conclusions: Adult hMSCs affect arrhythmicity of cultured myocardial tissue by heterocellular coupling leading to depolarization-induced conduction slowing and paracrine activity that slows repolarization. The extent of these detrimental effects depends on the number and distribution pattern of hMSCs. These results suggest that caution should be urged against potential adverse effects of MSC transplantation in myocardial tissue.
- © 2012 by American Heart Association, Inc.