Treatment of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue.
Treatment of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue.
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通过同种异体骨髓和胰腺组织移植治疗非肥胖糖尿病小鼠的 1 型糖尿病。
DOI：
10.1073/pnas.84.18.6555
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发表时间：
1987
影响因子：
11.1
通讯作者：
Ikehara,S
中科院分区：
文献类型：
--
作者：
Yasumizu,R;Sugiura,K;Iwai,H;Inaba,M;Makino,S;Ida,T;Imura,H;Hamashima,Y;Good,RA;Ikehara,S
非肥胖糖尿病（NOD）小鼠提供了1型糖尿病的模型。我们以前的研究表明，异基因骨髓移植（ABMT）可以预防和治疗NOD小鼠的胰岛炎和显性糖尿病。然而，ABMT不能单独用于治疗NOD小鼠的显性糖尿病，因为其胰岛已被完全破坏。为了提供产生胰岛素的细胞，将新生小鼠的胰腺组织与ABMT联合移植到肾包膜下。同时进行的《反弹道导弹条约》的目标如下。(i)它诱导对供体型主要组织相容性复合体决定簇的免疫耐受，并允许宿主接受来自骨髓供体的后续胰腺同种异体移植物。(ii)ABMT用正常的干细胞替代异常的干细胞。移植骨髓和新生胰腺后，NOD小鼠显示糖尿减少，在葡萄糖耐量试验中反应正常。免疫组化研究显示，在移植的胰腺移植物中存在成簇的含胰岛素的β细胞。ABMT可能成为治疗人类1型糖尿病的可行方法。
Non-obese diabetic (NOD) mice provide a model for type 1 diabetes mellitus. We previously showed that allogeneic bone marrow transplantation (ABMT) can prevent and treat insulitis and overt diabetes in NOD mice. However, ABMT alone could not be used to treat overt diabetes in NOD mice whose islets had been completely destroyed. To provide insulin-producing cells, pancreatic tissue from newborn mice was grafted under the renal capsules in combination with ABMT. The aims of concomitant ABMT are as follows. (i) It induces immunological tolerance to the donor-type major histocompatibility complex determinants and permits the host to accept subsequent pancreatic allografts from the bone marrow donor. (ii) ABMT replaces abnormal stem cells with normal stem cells. After transplantation of bone marrow plus newborn pancreas, NOD mice showed reduction of the glycosuria and a normal response in the glucose-tolerance test. Immunohistological study revealed the presence of clustered insulin-containing beta cells in the grafted pancreatic transplants. ABMT may become a viable treatment of established type 1 diabetes mellitus in humans.