Mesenchymal Stem Cell-Based Immunomodulation in Allogeneic Heterotopic Heart-Lung Transplantation

Mesenchymal stem cells are able to differentiate in various cell lineages and they have shown immunomodulatory\udproperties in vitro, altering the cytokine secretion profile of T helper, T effector and dendritic cells and stimulating\udnatural killer cells towards an anti-inflammatory and tolerant phenotype. In vivo they prolong skin allograft survival and\udmay decrease graft-versus-host disease after hematopoietic stem cell transplants. In this work we studied the effects\udof mesenchymal stem cell treatment in an allogeneic heterotopic heart-lung transplant model.\udThe following experimental groups were formed: A) Control B) Immunosuppressive therapy (Cyclosporine A) C)\udMesenchymal stem-cell intravenous infusion D) Mesenchymal stem-cell infusion plus immunosuppressive treatment.\udThe infusion of mesenchymal stem cells improved the mean graft survival up to 14.5±3.7 days with respect to\udthe control group (3±0.6 days). Treatment with Cyclosporine A plus mesenchymal stem cells (group D) produced a\udmean survival time of 18.25±4.9 days, and was not significantly different to the results for group B (21.75±3.5 days).\udFurthermore, in the immunosuppressive treatment and the mesenchymal stem cell treatment, histological analysis\udrevealed a reduction in the grade of rejection in heart and lung grafts. This decrease was most significant in group D.\udIn conclusion, mesenchymal stem cells alone or in combination with Cyclosporine A were able to prolong graft\udsurvival time. These data suggest that, in vivo, mesenchymal stem cells retain their ability, already shown in vitro, to\udsuppress lymphocyte activation and proliferation