Fluorocapsules allow in vivo monitoring of the mechanical stability of encapsulated islet cell transplants
Fluorocapsules allow in vivo monitoring of the mechanical stability of encapsulated islet cell transplants
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DOI：
10.1016/j.biomaterials.2019.119410
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发表时间：
2019-11-01
期刊：
影响因子：
14
通讯作者：
Bulte, Jeff W. M.
中科院分区：
文献类型：
--
作者：
Arifin, Dian R.;Kulkarni, Mangesh;Bulte, Jeff W. M.
使用胶囊化胰岛细胞疗法的临床试验很少，总体上令人失望。这部分是由于缺乏合适的方法来监测移植的微胶囊随时间的完整性与破裂。通过将全氟-15-冠-5-醚（PFC）（一种可通过F-19 MRI检测的生物惰性化合物）的乳液包埋到双海藻酸盐层（Ba 2+凝胶化的海藻酸盐微胶囊）中来合成氟胶囊。荧光胶囊为球形，表面光滑，平均直径为428 ± 52 μ m。移植到小鼠体内后，胶囊的F-19 MRI信号保持稳定长达90天，相当于完整荧光胶囊的总数。当用藻酸盐裂解酶使单藻酸盐层胶囊破裂时，F-19 MRI信号在4天内消失。对于植入自身免疫性NOD/ShiLtJ小鼠并在体内经受藻酸裂解酶诱导的囊破裂的表达氟包封的小鼠β TC 6胰岛素瘤细胞，F-19 MRI信号随着时间的推移而急剧下降，沿着生物发光成像信号的下降，生物发光成像信号用作体内细胞活力的量度。这些结果表明，维持包膜完整性对于保存移植细胞存活至关重要，其中F-19 MRI信号的降低可作为包膜胰岛细胞治疗即将失败的预测性成像替代生物标志物。
Clinical trials that have used encapsulated islet cell therapy have been few and overall disappointing. This is due in part to the lack of suitable methods to monitor the integrity vs. rupture of transplanted microcapsules over time. Fluorocapsules were synthesized by embedding emulsions of perfluoro-15-crown-5-ether (PFC), a bioinert compound detectable by F-19 MRI, into dual-alginate layer, Ba2+-gelled alginate microcapsules. Fluorocapsules were spherical with an apparent smooth surface and an average diameter of 428 +/- 52 mu m. After transplantation into mice, the F-19 MRI signal of capsules remained stable for up to 90 days, corresponding to the total number of intact fluorocapsules. When single-alginate layer capsules were ruptured with alginate lyase, the F-19 MRI signal dissipated within 4 days. For fluoroencapsulated luciferase-expressing mouse beta TC6 insulinoma cells implanted into autoimmune NOD/ShiLtJ mice and subjected to alginate-lyase induced capsule rupture in vivo, the F-19 MRI signal decreased sharply over time along with a decrease in bioluminescence imaging signal used as a measure of cell viability in vivo. These results indicate that maintenance of capsule integrity is essential for preserving transplanted cell survival, where a decrease in F-19 MRI signal may serve as a predictive imaging surrogate biomarker for impending failure of encapsulated islet cell therapy.