- Dr Ariela Benigni, Principal Investigator
- Dr Marina Morigi, Co-Investigator
- Dr Andrea Remuzzi, Co-Investigator
- Mario Negri Institute for Pharmacological Research, Bergamo, Italy
- Generation of New Blood Vessels and Immunomodulation without Drugs to Improve Survival of Islet Grafts
Diabetes is a major health problem, affecting millions of people worldwide. It is caused by the failure of the body’s insulin-producing cells, the pancreatic islets. Although diabetes can be treated by regular insulin injection, long-term treatment can lead to many debilitating side effects including blindness, kidney failure, cardiovascular disease and loss of limbs. A much better treatment option is to cure diabetes by transplanting islets from a human donor. One problem is that islets need to “grow” a new blood supply after they are transplanted into a new host. This is a slow process, and many of the transplanted islets die in the meantime because they are starved of oxygen and nutrients. Moreover, ideally, the objective of clinical islet transplantation is to cure diabetes mellitus without the need of chronic immunosuppressive drug therapy. Indeed, although immunosuppressive medications have made allograft possible, there are many potential side effects associated with their use, including risks of cancer and infections. In addition, many of the immunosuppressive drugs needed to prevent graft rejection turn out to be diabetogenic. Therefore, promotion of islet revascularization through locally increased expression of growth factors, such as vascular endothelial growth factor (VEGF), and induction of donor-specific tolerance (immunosuppression without the need of antirejection drugs) to islet grafts could facilitate the applicability of islet transplantation as a viable clinical therapy for diabetes. Bone marrow-derived mesenchymal stem cells (MSCs) are capable of releasing VEGF. These cells have also profound immunomodulatory function.
Thus, the aim of this project is to test the hypothesis that when MSCs are co-transplanted with pancreatic islets they form a biological barrier which supports islet engraftment by secreting growth factors and prevents graft rejection by eliminating or regulating the host immune response in diabetic rats. If successful, this strategy would allow implementation of the islet transplant program in humans opening new perspectives for this effective therapy to cure millions of people with diabetes.