Research Of Stem Cell Transplantation Desensitization Protocol In Sensitized Recipients

Alloantibodies can be generated by previous exposure to major histocompatibility(MHC)antigens(usually via blood transfusions,previous allografts or pregnancy)or can occur denovo after transplantation.Donor-specific alloantibodies(DSA)mediate hyperacute and acute antibody-mediated rejection(AMR),which can lead to early graft damage and loss,and are also associated with chronic AMR and reduced long-term graft survival.Such alloantibodies can be survival long-term and difficult to deplete.So desensitization treatment for sensitized recipients remain a major problem in the field of transplantation.The procedure of hematopoietic stem cell transplantation(HSCT)will keep expanding over the next decades.The application of autologous HSCT in nonmalignant disease will grow.Autologous HSCT has been applied in autoimmune disease such as:systemic lupus erythematosus,systemic sclerosis,autoimmune hepatitis and acute injury disease such as:Acute Myocardial Infarction.The purpose of this study is to reset immune system of sensitized rats through myeloid bone marrow cell transplantation.After destroying the maintaining of alloantibodies the antibody level of sensitized recipients decreased to reduce the happening of antibody-mediated rejection.This study provides mechanism and feasibility for clinical desensitization treatment.There are three parts in this study.Part ? Rats kidney transplantation antibody-mediated rejection animal modelPurpose:We build rats kidney transplantation antibody-mediated rejection animal model.Method:According to different immunosuppression protocol the animals were separated to five groups.Group(1):Lewis to Lewis(non-sensitized)syngenic transplant.Group(2):DA to Lewis(non-sensitized),saline treatment.Group(3):DA to Lewis(non-sensitized),tacrolimus lmg/kg.d.Group(4):DA to Lewis(sensitized),saline treatment.Group(5):DA to Lewis(sensitized),tacrolimus lmg/kg.d.(n=6 every group).Result:(1)After skin sensitization alloantibody(IgG)level keep high long-term.(2)Antibody-mediated rejection can't be suppressed through regular immunosuppression protocol.(3)That is specific in histology of antibody-mediated rejection.Part? Rats Sygenic bone marrow transplant modelPurpose:We built Sygenic bone marrow transplant model.Method:According to the dosage of total body irradiation(TBI)the rats were separated into 2 groups.Group(1):sublethal group(4cGy).Group(2):lethal group(11cGy).Result:(1)All of rats can survival after bone marrow transplantation in two groups.(2)Comparing with group1 body weight of group2 rats decreased significancely.(p<0.01)(3)Lymphocyte in lymphoid organ can be fully replaced of group 2.(4)More than 95%PBMCs of group2 rats derived from donor and this percentage can keep stable long-term.But less than 30%PBMCs of groupl rats derived from donor and this percentage decreased after 3 months.Part ? Study about desensitization protocolPurpose:Study about desensitization protocol.Method:There are 2 groups in this part.Group(1):3m after skin transplantation performed kidney transplantation without desensitization treatment(FK506 lmg/kg.d).Group(2):lm after skin sensitization with desensitization of syngenic bone marrow transplantation.2m later kidney transplantation was performed.Result:Result showed that survival rate of group2 significantly higher than group2.Alloantibody level can be decreased 77.29%in group2.Conclusion:After resetting immune system through myeloid bone marrow cell transplantation alloantibody level of sensitized recipients can be decreased and antibody-mediated rejection can be suppressed.