Islet cell replacement and transplantation immunology in a mouse strain with inducible diabetes.
Islet cell replacement and transplantation immunology in a mouse strain with inducible diabetes.
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DOI：
10.1038/s41598-022-13087-3
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发表时间：
2022-05-31
影响因子：
4.6
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中科院分区：
文献类型：
--
作者：
为了开发糖尿病的细胞疗法，需要改进的实验性糖尿病模型。在这里，我们介绍了B6RIP-DTR小鼠，这是一种在完全免疫功能动物中建立的实验性糖尿病模型。这些近交系小鼠含有H_2B主要组织相容性复合体，在胰岛β细胞中选择性地表达高亲和力的人白喉毒素受体，并且是Ptprca(CD45.1)等位基因纯合，而不是野生型Ptprcb(CD45.2)。单次注射白喉毒素后，100%的B6RIP-DTR小鼠迅速患上糖尿病，而将同种C57BL/6小鼠的胰岛移植后，这种情况无限期地逆转。相比之下，MHC不匹配的胰岛被迅速排斥，这种同种移植反应很容易通过血糖和移植物组织学来监测。在混合造血嵌合的B6RIP-DTR患者外周血中，CD45.2、BALB/c供血者的免疫细胞和宿主的CD45.1细胞经流式细胞仪检测均能很好地区分。B6 RIP-DTR小鼠可靠的糖尿病诱导性和其他特性为推进基于移植的胰岛替代和免疫调节治疗糖尿病的研究提供了重要的新工具。
Improved models of experimental diabetes are needed to develop cell therapies for diabetes. Here, we introduce the B6 RIP-DTR mouse, a model of experimental diabetes in fully immunocompetent animals. These inbred mice harbor the H2b major histocompatibility complex (MHC), selectively express high affinity human diphtheria toxin receptor (DTR) in islet β-cells, and are homozygous for the Ptprca (CD45.1) allele rather than wild-type Ptprcb (CD45.2). 100% of B6 RIP-DTR mice rapidly became diabetic after a single dose of diphtheria toxin, and this was reversed indefinitely after transplantation with islets from congenic C57BL/6 mice. By contrast, MHC-mismatched islets were rapidly rejected, and this allotransplant response was readily monitored via blood glucose and graft histology. In peripheral blood of B6 RIP-DTR with mixed hematopoietic chimerism, CD45.2 BALB/c donor blood immune cells were readily distinguished from host CD45.1 cells by flow cytometry. Reliable diabetes induction and other properties in B6 RIP-DTR mice provide an important new tool to advance transplant-based studies of islet replacement and immunomodulation to treat diabetes.
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影响因子：
29
作者：
Magnuson MA;Osipovich AB
通讯作者：
Osipovich AB
影响因子：
21.3
作者：
Cigliola V;Ghila L;Thorel F;van Gurp L;Baronnier D;Oropeza D;Gupta S;Miyatsuka T;Kaneto H;Magnuson MA;Osipovich AB;Sander M;Wright CEV;Thomas MK;Furuyama K;Chera S;Herrera PL
通讯作者：
Herrera PL
影响因子：
23.9
作者：
George, Benson M.;Kao, Kevin S.;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
8.8
作者：
Marfil-Garza, Braulio A.;Pawlick, Rena L.;Shapiro, A. M. James
通讯作者：
Shapiro, A. M. James
影响因子：
7.7
作者：
Muller, Yannick D.;Golshayan, Dela;Seebach, Joerg D.
通讯作者：
Seebach, Joerg D.