Elimination of insulitis and augmentation of islet beta cell regeneration via induction of chimerism in overtly diabetic NOD mice.
Elimination of insulitis and augmentation of islet beta cell regeneration via induction of chimerism in overtly diabetic NOD mice.
复制标题
通过诱导明显糖尿病 NOD 小鼠的嵌合状态消除胰岛炎并增强胰岛 β 细胞再生。
DOI：
10.1073/pnas.0611101104
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发表时间：
2007
影响因子：
11.1
通讯作者：
Zeng,Defu
中科院分区：
文献类型：
--
作者：
Zhang,Chunyan;Todorov,Ivan;Lin,Chia-Lei;Atkinson,Mark;Kandeel,Fouad;Forman,Stephen;Zeng,Defu
Type 1 diabetes in both humans and nonobese diabetic (NOD) mice results from autoreactive T cell destruction of insulin-producing β cells. Cure of type 1 diabetes may require both reversal of autoimmunity and regeneration of β cells. Induction of chimerism via allogeneic hematopoietic cell transplantation has been shown to reestablish tolerance in both prediabetic and diabetic NOD mice. However, it is unclear whether this therapy augments β cell regeneration. Furthermore, this procedure usually requires total body irradiation conditioning of recipients. The toxicity of total body irradiation conditioning and potential for graft-versus-host disease (GVHD) limit the application of allogeneic hematopoietic cell transplantation for treating type 1 diabetes. Here we report that injection of donor bone marrow and CD4+T cell-depleted spleen cells induced chimerism without causing GVHD in overtly diabetic NOD mice conditioned with anti-CD3/CD8 and that induction of chimerism in new-onset diabetic NOD mice led to elimination of insulitis, regeneration of host β cells, and reversal of hyperglycemia. Therefore, this radiation-free GVHD preventive approach for induction of chimerism may represent a viable means for reversing type 1 diabetes.
