Additive effect of transplantation of adult stem cells post-infarction on the cardiac perfusion in pigs treated with beta-blocker and angiotensin-converting enzyme inhibitor

The beneficial effects associated with intramyocardial injection of adult stem cells in rodents have not been consistently reproduced in larger animals and humans. We evaluated the dose of porcine adipose-tissue derived mesenchymal stem cells (pASC) to increase cardiac tissue perfusion in pigs treated with ace-inhibitors and β-blockers to mimic human management post-MI. Animals were subjected to LCx occlusion and 4 weeks after MI blinded randomized in 4 groups to receive intramyocardial injection of pASC (1, 2 and 4x10^6 pASC/Kg bw) or placebo. Real time myocardial perfusion echocardiography (RTMPE) was conducted using commercial microbubbles before injection and 4 weeks after treatment with pASC. Anatomopathological assessments were performed to evaluated MI area, LV remodeling. Eight weeks after MI, the pigs treated with the highest dose of pASC showed a significant increase of myocardial blood flow in both remote (3.9 times) and border zone (3.7 times) versus the other groups, which was also in agreement with the increase in vessel numbers (about 54 and 56%, respectively) compared to the other groups (p>0.05). Interestingly, the non-perfused area was reduced (up to 38%) and the thinning ratio was higher (25%) in the 4x10^6 pASC/Kg.bw group compared with placebo or the other cell groups. In addition, the percentage of immature (thin/green) collagen fibers was greater in group 4 than in the placebo animals. The highest dose of allogeneic pASCs did not elicit an increased cellular inflammatory response in LV. Altogether, we provide evidence that intramyocardial injection of allogeneic pASC post-MI did not elicit cellular inflammatory response and also it increased cardiac perfusion and vessel number when in highest dose, which may have contributed to attenuate the LV adverse remodeling 2 months after the MI.