Abstract 5330: Radiofrequency Catheter Ablation Mediated Targeting of Mesenchymal Stromal Cells to Selected Cardiac Regions
Sinus node dysfunction and high-degree heart block are the major causes for electronic pacemaker implantation. Recently, genetically modified mesenchymal stromal cells (MSCs) were demonstrated to generate pacemaker function in vivo, using open thoracotomy and direct injection of modified MSCs into the ventricular wall. Future clinical implementation essentially requires development of more gentle methods to apply stem cells to specific cardiac locations. We performed selective power-controlled radiofrequency catheter ablation (RFCA) with eight ablation pulses (30 W, 60 s each) to induce heat mediated lesions at the right cardiac auricles of 22 pigs. Allogeneic MSCs (5 x 105 cells per kg bodyweight) labeled with superparamagnetic iron oxide particles (SPIOs), were infused intravenously in 4 pigs one day after RFCA treatment and hearts were explanted 8 days later. Prussian blue-staining revealed high numbers of SPIO-labeled cells in areas surrounding the RFCA induced lesions carrying the MSC specific surface antigen CD44. Moreover, antibody staining of MSC-positive areas showed a low infiltration of monocytes. In an effort to quantify the number of migrated cells, we applied various concentrations of allongeneic human MSCs (105–107 cells/kg bodyweight) in 12 pigs. The number of migrated cells were calculated by quantitative Real-Time PCR using specific primers for human MSC detection. Strictly dependent on the number of human MSCs applied, up to 7 % of the cells appeared in the right cardiac auricle of RFCA-treated pigs. In non-targeted organs, human MSCs appeared at significantly lower levels. To assess the fate of MSC’s at targeted sites, right cardiac auricles of 6 pigs were analysed after 3 and 6 month by means of quantitative Real-Time PCR and Prussian-blue staining. The results revealed that 3 and 6 month after transplantation human MSCs were detectable, although at remarkably reduced levels. In summary, RFCA mediated targeting of MSCs provides a new strategy for cardiac stem cell application avoiding open thoracotomy and direct injection of cells. Results indicate an efficient guidance and longlasting residence of MSCs to myocardial sites closely related to the sinoatrial node providing an opportunity to rescue or induce pacemaker function.