Introduction: Cardiac atrial appendage stem cells have been shown to preserve cardiac function in the setting of acute myocardial infarction (MI) in the minipig model : this application takes advantage of preserved extracellular tissue architecture, although it is subject to the inflammatory hostility of the milieu.
Hypothesis: Whether this treatment is also applicable to a chronic ischemia model remains unknown.
Methods: Autologous CASCs were isolated from atrial appendages of Göttingen minipigs based on high aldehyde dehydrogenase activity and expanded. MI was induced by 2 h snare ligation of the left anterior descending artery. Two months (M) after MI induction, CASCs were intramyocardially injected under NOGA guidance (MI-CASC, n=6). Non-transplanted pigs (MI, n= 8) received sham treatment. 3D electromechanical mapping (EMM) and cardiac MRI were performed to assess left ventricular (LV) function.
Results: Global LV ejection fraction was preserved 2M post-injection in the MI-CASC group (57±13% pre vs 60±7% at 2M), whereas it decreased in the MI group (59±4% vs 40±7%, p=0.0002 MI-CASC vs MI). LVESV remained unchanged in the CASC-MI group (16±4 ml pre vs 16±5 ml at 2M) whereas it significantly increased in the MI group (14±3 ml vs 28±8 ml, p=0.003 MI-CASC vs MI). EMM showed decreased viability and wall motion in the LV for both groups at the time of injection, whereas 2M post-injection those parameters improved in the MI-CASC group only. This was confirmed by infarct size measurement on MRI (delayed enhancement) : in the MI-CASC group infarct size decreased from 6.2±2.0% to 3.7±1.0% of the LV mass, p=0.04, whereas in the MI group it remained unchanged (5.5±1.1% to 6.1±1.8%). Cell retention was accompanied by cardiomyogenic differentiation of transplanted CASCs, which integrated functionally.
Conclusion: CASC transplantation in the setting of a chronic MI is able to preserve cardiac function and therefore, prevent the occurrence of heart failure.