A prevascularized subcutaneous device-less site for islet and cellular transplantation
A prevascularized subcutaneous device-less site for islet and cellular transplantation
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DOI：
10.1038/nbt.3211
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发表时间：
2015-05-01
影响因子：
46.9
通讯作者：
Shapiro, A. M. James
中科院分区：
文献类型：
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作者：
Pepper, Andrew R.;Gala-Lopez, Boris;Shapiro, A. M. James
将供体来源的胰岛移植到肝脏中是糖尿病患者成功的细胞替代疗法。然而，由于几个原因，包括移植物磨损和不能取回或成像胰岛，肝血管不是最佳的移植部位。在这里，我们描述了胰岛移植到预先血管化的皮下部位，通过临时放置医学批准的血管通路导管创建。在链脲佐菌素（STZ）诱导的糖尿病小鼠中，将类似于500个同源胰岛移植到所产生的“无装置”空间中，91%的小鼠的糖尿病得到逆转，并保持正常血糖>100天。这种方法在患有糖尿病的小鼠中也有效，在另一种小鼠品系中，这种小鼠产生了更强烈的炎症反应，并且穿过了同种异体屏障。这些结果表明，皮下部位的瞬时引发支持小鼠模型中的糖尿病逆转胰岛移植，而不需要永久性细胞包封装置。
Transplantation of donor-derived islets into the liver is a successful cellular replacement therapy for individuals with diabetes. However, the hepatic vasculature is not an optimal transplant site for several reasons, including graft attrition and the inability to retrieve or image the islets. Here we describe islet transplantation into a prevascularized, subcutaneous site created by temporary placement of a medically approved vascular access catheter. In mice with streptozotocin (STZ)-induced diabetes, transplantation of similar to 500 syngeneic islets into the resulting 'device-less' space reversed diabetes in 91% of mice and maintained normoglycemia for >100 days. The approach was also effective in mice with pre-existing diabetes, in another mouse strain that mounts a more vigorous inflammatory response, and across an allogeneic barrier. These results demonstrate that transient priming of a subcutaneous site supports diabetes-reversing islet transplantation in mouse models without the need for a permanent cell-encapsulation device.