Intracardiac allogeneic mesenchymal stem cell transplantation elicits neo-angiogenesis in a fully immunocompetent ischaemic swine model.
OBJECTIVE
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 peri-infarct area (1×10(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 CD3+ 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.
Poncelet
Alain J
AJ
Laboratory of Experimental Surgery, Université catholique de Louvain, Faculté de Médecine, Avenue Hippocrate 55, 1200 Brussels, Belgium. Alain.Poncelet@uclouvain.be
Hiel
Anne-Lise
AL
Vercruysse
Jonathan
J
Hermans
Dominique
D
Zech
Francis
F
Gianello
Pierre
P
D000818:Animals; D002196:Capillaries / Q000473:pathology; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D007113:Immunity, Innate; D007121:Immunocompetence; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology; D009203:Myocardial Infarction / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D016559:Tacrolimus