Abstract 10862: Safety and Effectiveness of Innovative Tissue Therapy for Porcine Myocardial Infarction Using Autologous Skeletal-myobkast-sheets
Background: Autologous skeletal myoblast (SkM) injection has been used for repairing infracted myocardium. However, safety concerns of ventricular tachyarrhythmia have arisen from some clinical trials of SkM-injection therapy. This study examined the effect and safety of SkM sheet therapy in a pig model of chronic myocardial infarction.
Methods: Mini-pigs underwent LAD occlusion by a balloon catheter for 2 hours, followed by reperfusion. After 28 days, 12 SkM sheets were transplanted onto infarcted myocardium (Sheet-group n = 8), the same amount of cells were injected into the myocardium (Injection-group n = 7) and sham operations were performed as control (Sham-group n = 7). Implantable ECG loop recorder (ILR) was implanted subcutaneous on the left thorax. At 28 days after the transplantation, we assessed cardiac function with MDCT, interrogated ILR, and performed programmed ventricular stimulation (PVS); after which organs were harvested for histopathology. For assessing the inflammatory and injury response, inflammation factors, and high-sensitive CRP and Troponin-I were measured at 1, 3, 7, and 28 days after the transplantation by cytokine array method and ELISA, respectively.
Results: Sheet-group improved their cardiac function compared with the Injection-group and the Sham-group (LVEF change: 5.8 ± 2.7, -1.0 ± 2.6 and -3.8 ± 1.8 % in the Sheet, Injection and Sham-groups, respectively, P < 0.05 (ANOVA)). No VF was detected by ILR in all groups, while VT was detected in one pig of the Injection-group. The percentage of animals in which VF was induced was 25.0%, 71.4% and 28.6%, respectively. In the Injection-group, anti-macrophage positive cells were observed around the injected cells in the myocardium of the Injection-group. Transmission electron microscopic images demonstrated differentiated myofilaments, collagen layers and a characteristic extracellular matrix surrounds the SkMs In the sheet-group. Toroponin-I and IL-6 levels increase in the Injection-group compared with the Sheet and Sham-groups.
Conclusions: SkM sheets transplanted onto infarcted myocardium improved cardiac function over SkM injection without increasing arrhythmogenicity. Myocardium inflammation may increase the arrhythmia risk.
- © 2012 by American Heart Association, Inc.