Department of Translational Research & Cellular Therapeutics, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
Mol Imaging Biol. 2021 Apr;23(2):173-179. doi: 10.1007/s11307-020-01560-2. Epub 2020 Nov 2.
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.
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.
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.
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.
胰岛移植是治疗 1 型糖尿病的一种很有前途的细胞替代疗法。目前正在研究皮下胰岛移植作为规避标准肝内胰岛移植相关问题的一种手段。随着为提高皮下胰岛移植功效而进行的改良，拥有强大的方法来评估移植物的植入情况非常重要。在实验中，使用荧光素酶报告基因的 ATP 依赖性生物发光成像已被证明可用于非侵入性地跟踪植入情况。但是，此前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（移植的主要结果）相关。
使用从小鼠皮下胰岛移植中获得的数据进行了回顾性分析。该分析包括我们实验室进行的移植，其中胰岛供体是泛表达荧光素酶的转基因大鼠，而受体是野生型、链脲佐菌素诱导的糖尿病大鼠。在移植后观察期（长达 6 周）内，从 27 次胰岛移植中获得了 79 次生物发光扫描的数据。在静脉内给予荧光素后，对皮下移植的移植物的生物发光强度进行了检测，并与糖尿病逆转相关联。
在皮下移植后，胰岛的生物发光强度随时间推移而降低，在移植后 1 至 3 周时降低超过 50％。在移植后的早期（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，1 周和 2 周时的胰岛生物发光强度预测了成功的移植。但是，移植后晚期（≥4 周）的强度不能反映移植结果。
早期表达荧光素酶的胰岛的生物发光成像可以作为一种有用的工具，通过预测葡萄糖稳态的变化来预测皮下胰岛移植的成功。
