Study for improvement of islet cell transplantation by renal transplantation with micro cell chimerism

点击翻译按钮获取中文摘要

The most of the IDDM patients needs renal transplantation because of diabetic nephropathy even if their blood sugar level was strictly controlled by insulin therapy. Clinically, the simultaneous pancreas (organ) and renal transplantation is applied for this disease, but this therapy is very invasive and its complications are not rare. The more ideal therapy must be the islet transplantation with renal transplantation but its clinical application is still limited because of its strong rejection. Therefore, we clarify whether graft modification by inducing the recipient micro cell chimerism improve the graft survival in islet cell transplantation. Inbrecd rats, F344 and LEW were used for the donor and the recipient. Four weeks before kidney transplantation, the donor total body irradiation (TBI) was performed. One week after TBI, the recipient bone marrow cells and splenocytes were infused to the same donor (BMTX). the renal graft in which the recipients cell chimerism was induced by TBI and BMTX, is transplanted to the recipient before F344 islet cell transplantation. The islet survivals of non-chimerism group (rejection was judged by hyperglycemia) are 7 to 14 days, which is longer than those of the islet transplantation alone, the blood sugar level of each recipient were elevated over 500 mg/dl after rejection. On the other hands, the survival of chimerism group were 11 to 25 days, which suggests the more longer survival could be obtained by this procedures. Immunological tolerance by donor TBI and BMTX could induced by the chimeric graft. The ideal condition ; strength of irradiation, number of bone marrow cells and intervals between each therapy and transplantation is now under investigation. Moreover, mechanism will be clarified by investigating the relationships between the number/strength of micro cell chimerism and graft survivals.