Intracardiac allogeneic mesenchymal stem cell transplantation elicits neo-angiogenesis in a fully immunocompetent ischaemic swine model

Objectives: Autologous mesenchymal stem cell transplantation has been shown to improve myocardial function in ischaemic cardiomyopathy. We studied one hypothetical mechanism, neo-angiogenesis, using allogeneic mesenchymal stem cell transplantation in an ischaemic swine model. Methods: Allogeneic mesenchymal stem cells were injected in the pen-infarct area (1 x 10(6) cells kg(-1)) 2 weeks after myocardial infarction. Myocardial infarction alone (n = 3) served as a control group. In the myocardial infarction-mesenchymal stem cells group (n = 6), tacrolimus was given from day 0 to day 12. Capillary density and inflammatory/rejection processes (anti-factor VIII and anti-CD3/CD68 monoclonal antibodies, respectively) were compared between groups. Results: In scarred myocardium, capillary density was similar between both ischaemic groups: 15.4 (+/-15.3) and 14.7 (+/-15.2) vessel/field in myocardial infarction-mesenchymal stem cells and myocardial infarction-alone groups (non-significant). In viable myocardium adjacent to the infarction, capillary density was significantly increased in the myocardial infarction-mesenchymal stem cells group than in the myocardial infarction-alone group (p = 0.002). The number of infiltrating CO(3+) cells was equivalent in both myocardial infarction-alone and myocardial infarction-mesenchymal stem cells groups (CD3+: 8.6% vs 9.3%, non-significant). However, CD68+ cell infiltration was more prominent after mesenchymal stem cell transplantation (4.7% vs 2% in myocardial infarction alone, p<0.01). Conclusions: Allogeneic mesenchymal stem cell transplantation enhances angiogenesis after myocardial infarction. This effect is limited to the viable myocardium. Using a concomitant 12-day course of tacrolimus, no mesenchymal stem cell-specific cellular immune response was demonstrated. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.