Abstract 564: Xenograft of Human Mesenchymal Stem Cells to Canine Myocardial Infarction Model with or without Epicardial Pacing has no Immune Rejection, But Proarrhythmia and Sympathetic Nerve Sprouting
Background Cardiac resynchronization therapy reduces morbidity and mortality in patients with heart failure, and mesenchymal stem cells (MSC) transplantation has a potential for the improvement of ventricular function, especially in acute stage of myocardial infarction. However, the safety of combined left ventricular (LV) epicardial pacing (EpiP) and MSC transplantation in acute myocardial infarction (AMI) has not been studied.
Methods and Results We explored the safety of human MSC (hMSC) transplantation in 15 canine model of with or without AMI or LV EpiP. AMI was made by ligation of proximal left circumflex coronary artery in open chest canine model, and positioned EpiP electrode on the peri-infarct zone (DDD mode, 3.5 V, minimal AV delay 150 ms). Implantable cardioverter defibrillator (ICD) was implanted in right ventricular endocardium to monitor ventricular arrhythmia. hMSC (1x107 in 1 mL, 5 sites) were injected subepicardially 15 mm separated from pacing electrode. We compared hMSC+EpiP+AMI (n=5), hMSC+EpiP (n=5), hMSC only (n=5), and sham operation (n=1) by ICD egm analysis and immunohistochemistry after 4 weeks of survival. Results: 1. 80% of hMSC+EpiP+AMI group, 60% of hMSC+EpiP group, 40% of hMSC only group, and none of control revealed spontaneous ventricular tachyarrhythmia (VT) episodes in stored ICD egm, and 60%, 40%, 20%, and 0% of each group died suddenly at 5.3±6.6 days after surgery. 2. Human nucleolin positive hMSC with vimenting positive meosdermal differentiation were observed at the subepicardial peri-infarct zone without any evidence of immune rejection. 3. The hMSC transplanted hearts expressed higher density of tyrosine hydroxylase positive cardiac nerves compared with control dog.
Conclusion Although hMSC xenograft to canine AMI and EpiP model showed successful engraftment of hMSC without immune rejection, VT and sudden death with sympathetic hyper-innervation happened frequently.