Abstract 13580: Cardiac Atrial Appendage Stem Cells Preserve Cardiac Function in a Minipig Acute Myocardial Infarction Model
We assessed the hypothesis that cardiac function following acute myocardial infarction (MI) in the minipig model is preserved by autologous transplantation of the recently described cardiac atrial appendage stem cells (CASCs). Right atrial appendages from Göttingen minipigs were obtained through right minithoracotomy. CASCs were isolated based on high aldehyde dehydrogenase activity, green fluorescent protein (GFP) labeled and expanded until P9. After 2 months, an MI was induced by snare ligation of the LAD for 2h, followed by reperfusion. CASCs (n=109.106±159.106) were epicardially injected upon reperfusion in the treatment group (Tx, n=6), whereas controls (C, n=5) received medium only. Cardiac MRI was performed at baseline, post MI and at 2M. Control animals developed progressive ventricular dilatation: LVEDV 34±5ml post MI and 50±5ml at 2M, LVESV 15±1ml and 30+±4ml respectively. In the CASC group volumes remained constant: LVEDV 41±3ml post MI and 40±7ml at 2M (p=.046 vs C), LVESV 20±3ml and 22±7ml (p=.06 vs C) respectively. Consequently, global LVEF decreased by 15±7% in C vs 5±8% in CASCs (p=.049). Regional wall thickening in border areas (delayed enhancement) was significantly higher in Tx than in C. Immunohistochemistry of explanted hearts at 2M showed cardiomyogenic differentiation of transplanted CASCs, monitored as co-localization of GFP and sarcomerically organized troponin T using confocal microscopy. Effective sarcomere formation was confirmed by label-free second harmonic generation microscopy. Safety of CASC transplantation was shown by the absence of teratoma formation. All animals were implanted with event recorders (Medtronic-Reveal®) between post MI and 2M MRI scans. No episodes of ventricular tachyarrhytmias were recorded. In conclusion, CASCs preserve cardiac function, based on cardiomyogenic differentiation. Absence of safety issues makes them a suitable candidate for a phase I clinical trial.
- © 2013 by American Heart Association, Inc.