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

微细胞嵌合肾移植改善胰岛细胞移植的研究

基本信息

批准号：
11671148
负责人：
FURUYA Tomoki
金额：
$ 2.3万
依托单位：
Akita University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671148/
关键词：
Islet cell transplantation Bone marrow transplantation Total body irradiation kidney transplantation

项目摘要

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.

尽管胰岛素治疗严格控制了血糖水平，但大多数IDDM患者仍因糖尿病肾病而需要肾移植。临床上采用胰（器官）肾联合移植治疗，但该方法创伤性大，并发症也不少见。目前较为理想的治疗方法是胰岛联合肾移植，但由于其排斥反应强，临床应用受到限制。因此，我们阐明了在胰岛细胞移植中，通过诱导受体微细胞嵌合体的移植物修饰是否改善了移植物存活。供体和受体分别采用近交系大鼠、F344和LEW。在肾移植前4周，进行供体全身照射（TBI）。TBI后1周，将受者骨髓细胞和脾细胞输注给同一供体（BMTX）。在F344胰岛细胞移植之前，将其中受体细胞嵌合由TBI和BMTX诱导的肾移植物移植到受体。非嵌合体组（以高血糖判断排斥反应）胰岛存活时间为7 ~ 14 d，较单纯胰岛移植组长，排斥反应后血糖均升高500 mg/dl以上。而嵌合体组的存活时间为11 ~ 25天，提示该方法可获得更长的存活时间。嵌合移植物可诱导对供体TBI和BMTX的免疫耐受。理想状态;照射强度、骨髓细胞数量和每次治疗与移植之间的间隔正在研究中。此外，机制将通过研究微细胞嵌合体的数量/强度与移植物存活率之间的关系来阐明。