Abstract 5329: A Novel Technology to Prevent Proarrhythmia of Myoblast Transplantation: “Patterning” of Cell Alignment Using Magnetic Nanoparticles
Purpose: Autologous transplantation of skeletal myoblasts (SkMBs) has been expected as a promising strategy to treat severe heart failure, but its feasibility is limited by lethal arrhythmias. We hypothesized that transplantation of SkMBs with “patterned” cell alignment, instead of “random” injection, could be a novel approach to solve this problem.
Methods: Human SkMBs were labeled using magnetite nanoparticles with cationic liposomes and co-cultured with rat neonatal cardiomyocytes (CMs) on a dish with 64 electrodes to record extracellular excitation. Patterning of SkMBs was carried out using a linear magnet placed beneath the culture dish.
Results: In control (culture of CM alone), stable excitations were propagated uniformly. In injection model (co-culture without patterning), where SkMBs were dispersed randomly among CMs, asynchronous excitations of multiple origins propagated inhomogeneously. In patterning model (co-culture with patterning), where a linear alignment of SkMBs was inserted into CM monolayer, well-organized propagation of stable excitation was preserved, although it was distorted by unexcitable barrier of SkMBs. Conduction velocity was significantly decreased in injection model (48.1±25.9 μm/ms, p<0.01, n=5) compared to control (285.6±254.5 μm/ms, n=7), whereas there was no significant change in patterning model (209.7±110.3 μm/ms, p=0.12, n=5). Automaticity was evaluated by inter-beat interval (IBI) of spontaneous beats. In injection model, IBI and its standard deviation (SD) were significantly increased (2303±2026 ms, p<0.01, n=5) compared to control (763±280 ms, n=7). In contrast, there was no significant change in patterning model (1132±211 ms, p=0.29, n=5). These results may be ascribed to different microscopic structural heterogeneity in two models. Expression of gap junction (connexin43) was not detected between CM and SkMB by immunofluorescent staining..
Conclusion: Patterned transplant of SkMBs to CMs resulted in more organized propagation of excitation without creating substrates for microscopic reentry. The result suggests that cell patterning using magnetic nanoparticles could provide a novel approach to prevent lethal arrhythmias in association with SkMB transplant therapy.