The Laboratory deals with the identification of new strategies and therapeutic targets for modulating innate and adaptive immune response toward the graft and for promoting the induction of transplantation tolerance. The immunomodulatory potential of new pharmaceutical agents or innovative cellular therapy is tested in experimental models of kidney, heart and lung transplantation with the aim to design the best protocol for future clinical application.
The Laboratory is also involved in the identification of immune dysregulation processes in immune-mediated renal diseases.
Cellular therapy with mesenchymal stromal cells in transplantation
Mesenchymal stromal cells are adult stem cells with unique immunomodulatory capabilities. In transplant models a single MSC infusion induced indefinite survival of kidney and heart allografts. We are conducting pilot clinical studies with MSC in kidney transplant patients with a living- or deceased- donors and in liver transplant recipients. Preliminary results are very promising and suggest that the MSC therapy can induce, in selected patients, a state of operational tolerance, i.e. a stable graft function in the absence of immunosuppressive therapy.
Novel anti-rejection strategies for lung transplantation
The outcomes of lung transplant largely lag behind that for other solid organ transplants due to a more aggressive acute rejection toward lung grafts compared to that against the kidney or the heart. This is probably due to the constant exposure of transplanted lungs to environmental stimuli that trigger innate immune cell activation. We recently set up a lung transplant models in rats and are currently evaluating the efficacy of both novel compounds such as an IL-8 receptor inhibitor and of immunomodulatory cell therapies.
Immune cell dysregulation in renal diseases
Immune-mediated renal diseases including membranous nephropathy and nephrotic syndrome, are probably caused by a dysregulation of the immune cells. Membranous nephropathy (MN) is characterized by the development of autoantibodies against renal proteins that, once locally deposited, caused the renal disease. Nephrotic syndrome (NS)is characterized by alteration of renal structures that lead to massive protein loss with the urine, reduction of plasma protein levels and edema. Both MN and NS are treated with immunosuppressive drugs. We are deeply evaluating the phenotype of circulating immune cells in these patients with the aim to detect immune cell dysregulation and possibly identify new therapeutic targets.
Ischemia/reperfusion Injury in kidney transplantation
In kidney transplantation, ischemia/reperfusion is an inevitable cause of tissue damage, which has serious consequences for the patient and for which there is currently no cure. In the immediate post-transplant, ischemia/reperfusion injury exposes the patient to the risk of delayed graft function and acute rejection, whereas, in the long term, to the increased risk of chronic graft rejection. We are studying the mechanisms underlying the ischemia/reperfusion injury with a particular interest on the role of the innate immune system cells, resident in the transplanted kidney, to find out new therapies to contrast ischemia/reperfusion injury.
Novel anti-rejection strategies for lung transplantation
The outcomes of lung transplant largely lag behind that for other solid organ transplants due to a more aggressive acute rejection toward lung grafts compared to that against the kidney or the heart. This is probably due to the constant exposure of transplanted lungs to environmental stimuli that trigger innate immune cell activation. We recently set up a lung transplant models in rats and the ex-vivo lung perfusion technique. We are currently evaluating the efficacy of mesenchymal stromal cells given to recipients as immunomodulatory therapy and administered during the lung perfusion as a pro-reparative therapy.
International Consensus on Cardiopulmonary Resuscitation.
