Pancreatic Tissue Transplanted in TheraCyte™ Encapsulation Devices Is Protected and Prevents Hyperglycemia in a Mouse Model of Immune-Mediated Diabetes
Pancreatic Tissue Transplanted in TheraCyte™ Encapsulation Devices Is Protected and Prevents Hyperglycemia in a Mouse Model of Immune-Mediated Diabetes
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DOI：
10.3727/096368915x688939
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发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
von Herrath, Matthias
中科院分区：
文献类型：
--
作者：
Boettler, Tobias;Schneider, Darius;von Herrath, Matthias
1型糖尿病（T1 D）的特征在于葡萄糖响应性产生胰岛素的胰腺β细胞的破坏，并表现出胰岛的免疫浸润，其中CD 8淋巴细胞最突出。胰岛的治愈性移植受到自身反应性免疫细胞持续存在的严重阻碍，需要高剂量的免疫抑制药物。一个优雅的方法来赋予移植物保护，同时避免免疫抑制的需要是使用封装设备，允许氧气和营养物质的转移，但防止免疫细胞与胰岛移植物直接接触。在这里，我们证明了装载有新生胰腺组织并移植到RIP-LCMV.GP小鼠中的巨囊化装置（TheraCyte（TM））在病毒诱导的糖尿病模型中预防疾病发作。组织学分析显示，在糖尿病动物模型中，产生胰岛素的细胞在装置内存活。我们的研究结果表明，这些封装装置可以保护免受免疫介导的攻击，并可以包含足够量的胰岛素产生细胞，以防止明显的高血糖症。
Type 1 diabetes (T1D) is characterized by destruction of glucose-responsive insulin-producing pancreatic beta-cells and exhibits immune infiltration of pancreatic islets, where CD8 lymphocytes are most prominent. Curative transplantation of pancreatic islets is seriously hampered by the persistence of autoreactive immune cells that require high doses of immunosuppressive drugs. An elegant approach to confer graft protection while obviating the need for immunosuppression is the use of encapsulation devices that allow for the transfer of oxygen and nutrients, yet prevent immune cells from making direct contact with the islet grafts. Here we demonstrate that macroencapsulation devices (TheraCyte (TM)) loaded with neonatal pancreatic tissue and transplanted into RIP-LCMV.GP mice prevented disease onset in a model of virus-induced diabetes mellitus. Histological analyses revealed that insulin-producing cells survived within the device in animal models of diabetes. Our results demonstrate that these encapsulation devices can protect from an immune-mediated attack and can contain a sufficient amount of insulin-producing cells to prevent overt hyperglycemia.