- Dr. Marina Noris, Principal Investigator
- Prof. Giuseppe Remuzzi, Co-Investigator
- Dr. Carlo Alberto Redi, Co-Investigator
- Dr. Maurizio Zuccotti, Co-Investigator
- Mario Negri Institute for Pharmacological Research, Bergamo, Italy
- Donor Stem Cell Infusion to Induce Allospecific Graft Tolerance
Donor-specific tolerance, defined as a state of systemic non-responsiveness to an allograft without the need for anti-rejection drugs is becoming increasingly the 'holy grail' of transplant physicians. Transplantation of allogeneic hematopoietic cells into irradiated hosts can lead to life-long donor-specific chimerism that is linked with permanent tolerance of donor organs or tissue transplants. In this regard, we recently documented that pre-transplant infusion of donor bone marrow cells or donor peripheral blood leukocytes into rats allowed indefinite survival of a subsequent kidney allograft. The above strategies however, expose graft recipients to the risk of graft-versus-host disease (GVHD). In addition, donor MHC-mismatched hematopoietic grafts are usually acutely rejected unless the host is vigorously myeloablated or immunosuppressed. Data are now emerging that the use of donor embryonic stem cells would circumvent the above hurdles. Given their immature immunological status these cells would not cause GVHD and would circumvent acute rejection of the allospecific immune response of the recipient. However, the use of embryonic-derived stem cells is still far from being clinically applicable to solid organ transplantation, due to strong ethical issues and the limited availability of embryo-derived stem cells and solid organ grafts from the same donor. On the other hand, a large number of totipotent stem cells could be acquired by the ‘nuclear transfer’ technique, which consists of the genetic re-programming of the nucleus of the somatic differentiated cell. In this project we will assess in a mouse model of heart allografts, whether donor stem cells derived by ‘nuclear transfer can be applied to induce tolerance after solid organ transplantation.