Abstract 1694: Human Ventricular Scar Fibroblasts do Not Conduct Electrical Current over Considerable Distances in an Experimental Conduction Block in Cardiomyocyte Cultures in Contrast to Mesenchymal Stem Cells from Ischemic Heart Disease Patients.
Introduction: Scar formation after myocardial infarction is associated with slow conduction and conduction block, thereby increasing the risk of arrhythmias. Cell therapy aiming to reconstitute ventricular scar tissue may improve cardiac function and lower arrhythmogenic potential.
Aim: To assess the ability of human ventricular scar derived fibroblasts (hVSFs) and bone-marrow derived human adult mesenchymal stem cells (hMSCs) from ischemic heart disease (IHD) patients to conduct electrical current, thereby repairing conduction blocks in cardiomyocyte cultures.
Material and Methods: Neonatal rat cardiomyocytes (CMCs) were cultured in multi electrode arrays (Multi Channel Systems, Germany), resulting in a spontaneously and synchronously beating monolayer. After 2 days, a central conduction block was created by abrasion of a 320±30 μm wide channel, dividing the monolayer in two asynchronously beating CMC fields. Then, either 50x103 GFP-labeled hVSFs or 50x103 GFP-labeled hMSCs were applied in the channel. As control, 50x103 DiI-labeled CMCs or no cells were applied. Electrical conduction across the channel was assessed 24 h after application of cells. Immunostaining was carried out for connexin43 (Cx43) and SCN5A, encoding cardiac sodium channel.
Results: Within 24 h, electrical conduction between the two CMC fields was restored by either hMSCs (n=8) or CMCs (n=9), with an electrical conduction velocity (CV) of 1.3±0.8 cm/s and 16.9±0.8 cm/s, respectively. In contrast, hVSFs did not repair conduction blocks (n=6, p<0.01), associated with persistent asynchronously beating CMC fields. Resynchronization did not occur in the absence of seeded cells (n=9). Cx43 was present between adjacent hMSCs, CMCs, or hVSFs, as well as between CMCs adjacent to either one of the two cell types. In hVSFs Cx43 staining showed a more punctuated pattern. No SCN5A staining was found, except in CMCs.
Conclusions: Human ventricular scar derived fibroblasts can not conduct electrical current and repair conduction blocks over considerable distances, explaining the functional block and slowing in conduction observed in scarred myocardium. In contrast, mesenchymal stem cells from IHD patients can repair conduction block, probably through electrotonic interaction.