- Dr. David Sachs, Principal Investigator
- Dr. Kazuhiko Yamada, Co-Investigator
- Massachusetts General Hospital, Boston, USA
- Thymic Transplantation to Achieve Tolerance
One of the major limitations to the field of transplantation today is the insufficient supply of donor organs. The current proposal is directed toward the eventual goal of making it possible to transplant organs from other species (a procedure called "xenotransplantation") in order to overcome this limitation.
Our plans involve transplantation of the thymus, which is the lymphoid tissue of greatest importance in the immune response to transplantation. The thymus is the site where new immune cells, which are continuously formed throughout life, are selected not to react against "self", which would otherwise cause autoimmune disease. The result of this selection is called immunologic tolerance. Because the immune response across species is extremely strong, we hope to induce tolerance to xenotransplants, rather than relying on very high doses of immunosuppressive drugs, which would have serious side effects.
We will transplant the thymus of donor animals to potential recipients, in an attempt to induce tolerance to other tissues and organs from the same donor. It is known that transplants of tissues like the thymus are more readily accepted if they have their own blood supply than if they must establish new blood vessels from the recipient in order to survive. For this reason, we will transplant composite organs into which the donor animal’s own thymic tissue has been implanted several months prior to the organ transplant. This procedure gives the thymus tissue sufficient time to heal in, so that when organ transplantation is performed, the thymus does not need additional time to become vascularized.
We have already shown in miniature swine that this process is successful across limited transplant barriers within a species. We will now try to apply it to highly mismatched transplants within this species, as well as from swine to baboons, a species barrier that is very relevant for eventual clinical xenotransplantation.