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Islet transplantation in the subcutaneous space achieves long-term euglycaemia in preclinical models of type 1 diabetes.
Nature Metabolism ( IF 20.8 ) Pub Date : 2020-09-07 , DOI: 10.1038/s42255-020-0269-7
Ming Yu 1 , Divyansh Agarwal 1, 2 , Laxminarayana Korutla 1 , Catherine L May 3, 4 , Wei Wang 1 , Negin Noorchashm Griffith 5 , Bernhard J Hering 6 , Klaus H Kaestner 3 , Omaida C Velazquez 7 , James F Markmann 8 , Prashanth Vallabhajosyula 9 , Chengyang Liu 1 , Ali Naji 1, 3
Affiliation  

The intrahepatic milieu is inhospitable to intraportal islet allografts1,2,3, limiting their applicability for the treatment of type 1 diabetes. Although the subcutaneous space represents an alternate, safe and easily accessible site for pancreatic islet transplantation, lack of neovascularization and the resulting hypoxic cell death have largely limited the longevity of graft survival and function and pose a barrier to the widespread adoption of islet transplantation in the clinic. Here we report the successful subcutaneous transplantation of pancreatic islets admixed with a device-free islet viability matrix, resulting in long-term euglycaemia in diverse immune-competent and immuno-incompetent animal models. We validate sustained normoglycaemia afforded by our transplantation methodology using murine, porcine and human pancreatic islets, and also demonstrate its efficacy in a non-human primate model of syngeneic islet transplantation. Transplantation of the islet–islet viability matrix mixture in the subcutaneous space represents a simple, safe and reproducible method, paving the way for a new therapeutic paradigm for type 1 diabetes.



中文翻译:

皮下空间中的胰岛移植在 1 型糖尿病的临床前模型中实现了长期血糖正常。

肝内环境不适合门静脉内胰岛移植物1,2,3,限制了它们治疗 1 型糖尿病的适用性。尽管皮下空间代表了胰岛移植的替代、安全且易于接近的部位,但缺乏新血管形成和由此导致的缺氧细胞死亡在很大程度上限制了移植物存活和功能的寿命,并对胰岛移植在胰岛移植中的广泛采用构成了障碍。诊所。在这里,我们报告了胰岛与无装置胰岛活力矩阵混合的成功皮下移植,从而在各种免疫功能正常和免疫功能低下的动物模型中产生长期血糖正常。我们使用鼠、猪和人胰岛验证了我们的移植方法提供的持续正常血糖,并且还证明了其在同基因胰岛移植的非人类灵长类动物模型中的功效。在皮下空间移植胰岛 - 胰岛活力基质混合物代表了一种简单、安全和可重复的方法,为 1 型糖尿病的新治疗范式铺平了道路。

更新日期:2020-09-08
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