Technologies et recherche en matière de transplantation

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

Abstract

Biancamaria Longoni, Erzsèbet Szilàgyi, Lorenza Puviani, Benedetta Mazzanti, Giacomo Timoteo Paoli, Serena Urbani, Paola Quaranta, Sara Antonini, Sergio Tripodi, Marcella Cintorino, Riccardo Saccardi, Bruno Nardo and Franco Mosca

Mesenchymal stem cells are able to differentiate in various cell lineages and they have shown immunomodulatory properties in vitro, altering the cytokine secretion profile of T helper, T effector and dendritic cells and stimulating natural killer cells towards an anti-inflammatory and tolerant phenotype. In vivo they prolong skin allograft survival and may decrease graft-versus-host disease after hematopoietic stem cell transplants. In this work we studied the effects of mesenchymal stem cell treatment in an allogeneic heterotopic heart-lung transplant model.

The following experimental groups were formed: A) Control B) Immunosuppressive therapy (Cyclosporine A) C) Mesenchymal stem-cell intravenous infusion D) Mesenchymal stem-cell infusion plus immunosuppressive treatment.

The infusion of mesenchymal stem cells improved the mean graft survival up to 14.5±3.7 days with respect to the control group (3±0.6 days). Treatment with Cyclosporine A plus mesenchymal stem cells (group D) produced a mean survival time of 18.25±4.9 days, and was not significantly different to the results for group B (21.75±3.5 days). Furthermore, in the immunosuppressive treatment and the mesenchymal stem cell treatment, histological analysis revealed a reduction in the grade of rejection in heart and lung grafts. This decrease was most significant in group D.

In conclusion, mesenchymal stem cells alone or in combination with Cyclosporine A were able to prolong graft survival time. These data suggest that, in vivo, mesenchymal stem cells retain their ability, already shown in vitro, to suppress lymphocyte activation and proliferation.