Fluorocapsules for Improved Function, Immunoprotection, and Visualization of Cellular Therapeutics with MR, US, and CT Imaging
Fluorocapsules for Improved Function, Immunoprotection, and Visualization of Cellular Therapeutics with MR, US, and CT Imaging
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DOI：
10.1148/radiol.10092339
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发表时间：
2011-01-01
期刊：
影响因子：
19.7
通讯作者：
Bulte, Jeff W. M.
中科院分区：
文献类型：
--
作者：
Barnett, Brad P.;Ruiz-Cabello, Jesus;Bulte, Jeff W. M.
目的：开发新型免疫保护性藻酸盐微囊制剂，其中含有全氟化碳(PFC)，可增强细胞功能，为移植细胞提供免疫保护，同时使多模式成像成为可能。材料和方法：所有动物实验均由机构动物护理和使用委员会批准。用海藻酸盐、聚L赖氨酸、全氟辛基溴或全氟聚醚包裹人身体胰岛细胞。在2周内测定胰岛素的体外存活率和葡萄糖刺激指数，并用横截面时间序列回归模型进行分析。对包埋在凝胶模体中的氟胶囊进行了多模式(计算机断层扫描[CT]、超声[US]和氟19[F-19]磁共振[MR]成像)检测的灵敏度测定。C57BL/6小鼠接受6000PFOB标记(n=6)或6000PFPE标记的胰岛(n=6)，对照组小鼠接受6000PFOB(n=6)或6000 PFPE(n=6)标记的不含胰岛的氟胶囊，在55天内监测人C肽(胰岛素)的分泌。小鼠接受了9.4T的F-19磁共振成像和微CT扫描。猪(n=2)经肾动脉插管接受9000粒PFOB胶囊，用临床多层螺旋CT扫描。结果：与未加氟的海藻酸盐微囊相比，PFOB氟胶囊可促进人胰岛胰岛素的分泌，在8 mmol/L葡萄糖浓度下培养7d，胰岛素分泌量可达18.5%(3.78vs3.19)(P<；.001)。将免疫保护的微囊化细胞植入小鼠体内后，胰岛素得到持续释放，人C肽水平分别为19.1pmo1/L+/-0.9(标准差)和33.0pmol/L+/-1.0pmo1/L+/-1.0。结论：氟胶囊可增强体外葡萄糖反应和胰岛素分泌，可使异种胰岛细胞在体内长期分泌胰岛素，是一种新型的多模式成像造影剂平台。(C)RSNA，2010年
Purpose: To develop novel immunoprotective alginate microcapsule formulations containing perfluorocarbons (PFCs) that may increase cell function, provide immunoprotection for xenografted cells, and simultaneously enable multimodality imaging.Materials and Methods: All animal experiments were approved by an Institutional Animal Care and Use Committee. Cadaveric human islet cells were encapsulated with alginate, poly-L-lysine, and perfluorooctyl bromide (PFOB) or perfluoropolyether (PFPE). In vitro viability and the glucose-stimulation index for insulin were determined over the course of 2 weeks and analyzed by using a cross-sectional time series regression model. The sensitivity of multimodality (computed tomography [CT], ultrasonography [US], and fluorine 19 [F-19] magnetic resonance [MR] imaging) detection was determined for fluorocapsules embedded in gel phantoms. C57BL/6 mice intraperitoneally receiving 6000 PFOB-labeled (n = 6) or 6000 PFPE-labeled (n = 6) islet-containing fluorocapsules and control mice intraperitoneally receiving 6000 PFOB-labeled (n = 6) or 6000 PFPE-labeled (n = 6) fluorocapsules without islets were monitored for human C-peptide (insulin) secretion during a period of 55 days. Mice underwent F-19 MR imaging at 9.4 T and micro-CT. Swine (n = 2) receiving 9000 PFOB capsules through renal artery catheterization were imaged with a clinical multidetector CT scanner. Signal intensity was evaluated by using a paired t test.Results: Compared with nonfluorinated alginate microcapsules, PFOB fluorocapsules increased insulin secretion of encapsulated human islets, with values up to 18.5% (3.78 vs 3.19) at 8-mmol/L glucose concentration after 7 days in culture (P < .001). After placement of the immunoprotected encapsulated cells into mice, a sustained insulin release was achieved with human C-peptide levels of 19.1 pmol/L +/- 0.9 (standard deviation) and 33.0 pmol/L +/- 1.0 for PFPE and PFOB capsules, respectively. Fluorocapsules were readily visualized with F-19 MR imaging, US imaging, and CT with research-and clinical-grade imagers for all modalities.Conclusion: Fluorocapsules enhance glucose responsiveness and insulin secretion in vitro, enable long-term insulin secretion by xenografted islet cells in vivo, and represent a novel contrast agent platform for multimodality imaging. (C) RSNA, 2010