Purpose

The transplantation of pancreatic islets is a promising cell replacement therapy for type 1 diabetes. Subcutaneous islet transplantation is currently under investigation as a means to circumvent problems associated with standard intra-hepatic islet transplantation. As modifications are being developed to improve the efficacy of subcutaneous islet transplantation, it is important to have robust methods to assess engraftment. Experimentally, ATP-dependent bioluminescence imaging using luciferase reporter genes has been effective for non-invasively tracking engraftment. However, it was heretofore unknown if the bioluminescence of subcutaneously transplanted luciferase-expressing islet grafts correlates with diabetes reversal, a primary outcome of transplantation.

Procedures

A retrospective analysis was conducted using data obtained from subcutaneous islet transplantations in Lewis rats. The analysis included transplantations from our laboratory in which islet donors were transgenic rats ubiquitously expressing luciferase and recipients were wild type, streptozotocin-induced diabetic rats. Data from 79 bioluminescence scans were obtained from 27 islet transplantations during the post-transplant observation period (up to 6 weeks). The bioluminescence intensity of the subcutaneously transplanted grafts, captured after the intravenous administration of luciferin, was correlated with diabetes reversal.

Results

After subcutaneous transplantation, islet bioluminescence decreased over time, dropping > 50 % from 1 to 3 weeks post-transplant. Bioluminescence intensity in the early post-transplant phase (1–2 weeks) correlated with the subsequent reversal of diabetes; based on optimized bioluminescence cutoff values, the bioluminescence intensity of islets at 1 and 2 weeks predicted successful transplantations. However, intensity in the late post-transplant phase (≥ 4 weeks) did not reflect transplantation outcomes.

Conclusions

Early-phase bioluminescence imaging of luciferase-expressing islets could serve as a useful tool to predict the success of subcutaneous islet transplantations by preceding changes in glucose homeostasis.

中文翻译：

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胰岛移植物的早期荧光素酶信号预测大鼠皮下部位移植成功

目的

胰岛移植是一种很有前途的 1 型糖尿病细胞替代疗法。目前正在研究皮下胰岛移植作为规避与标准肝内胰岛移植相关问题的一种手段。随着正在开发修改以提高皮下胰岛移植的功效，重要的是要有可靠的方法来评估植入。在实验上，使用荧光素酶报告基因的 ATP 依赖性生物发光成像对于非侵入性跟踪植入是有效的。然而，迄今为止尚不清楚皮下移植的表达荧光素酶的胰岛移植物的生物发光是否与糖尿病逆转相关，糖尿病逆转是移植的主要结果。

程序

使用从 Lewis 大鼠皮下胰岛移植获得的数据进行回顾性分析。分析包括来自我们实验室的移植，其中胰岛供体是普遍表达荧光素酶的转基因大鼠，受体是野生型、链脲佐菌素诱导的糖尿病大鼠。在移植后观察期（长达 6 周）期间，从 27 例胰岛移植中获得了 79 次生物发光扫描的数据。静脉注射荧光素后捕获的皮下移植移植物的生物发光强度与糖尿病逆转相关。

结果

皮下移植后，胰岛生物发光随时间减少，移植后 1 至 3 周下降 > 50%。移植后早期（1-2 周）的生物发光强度与随后的糖尿病逆转相关；基于优化的生物发光截止值，胰岛在 1 周和 2 周的生物发光强度预测移植成功。然而，移植后晚期（≥ 4 周）的强度并不能反映移植结果。

结论

表达荧光素酶的胰岛的早期生物发光成像可以作为一种有用的工具，通过预先改变葡萄糖稳态来预测皮下胰岛移植的成功。