Induction of immunotolerance using non-myeloablating stem cell transtplantation in swine model of small intestinal transplantation

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Survival rate after Small intestinal transplantation has been improved gradually in recent 10 years. However, incidence of acute as well as chronic rejection is still high, and late graft loss is sometimes happen. In order to overcome immunological obstacles, induction of tolerance is called for.Non-myeloablating stem cell transplantation has been introduced as treatment tool for leukemia. In living-related organ transplantation, donor specific tolerance can be induced by this method. After tolerance induction by stem cell transplantation, small intestinal graft from the same donor can be accepted without immunosuppression. We have starting to establish this method using mini-swine model of small intestinal transplantation.In the first year, operion technique of small intestinal transplantation, using miniature swine was established. Ileal graft was harvested with pedicle. Cutting site of each superior mesenteric vessel was radix of celiac trunks and portal vein. Then graft was anastosed to Aorta and graft vein was anastomosed to IVC by end-to-side fashion.In the second year, non-myeloablating stem cell transplantation was started. Bone marrow cells were harvested from iliac bone. However the number of cells were not enough for tstem cell transplantation. Then we started irrigation of bone marrow, using two needle. After that the number of cells were increased. The numbers were identified by CD34 immunostaining.In the third year, miniature swine, SLA established syngenic chrone, cannot be supplied by animal farm. Especially, combination of SLA 1 mismatch is impossible now. We have proposed the protochol of chemotherapy which can establish the non-myelloablating protochol.