Microcapsules with intrinsic barium radiopacity for immunoprotection and X-ray/CT imaging of pancreatic islet cells

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• 作者：Dian R. Arifin^a ; ^b ; Sameer Manek^a ; ^b ; ^c ; Emma Call^a ; Aravind Arepally^a ; Jeff W.M. Bulte^a ; ^b ; ^c ; ^d ; ^{jwmbulte@mri.jhu.edu}
• 关键词：Microcapsule ; Islet cell ; Diabetes ; CT imaging ; Barium
• 刊名：Biomaterials
• 出版年：2012
• 期刊代码：7_01429612
• 类别：ms
• 出版时间：June, 2012
• 卷：33
• 期：18
• 页码：4681-4689
• 文件大小：1116 K

摘要

Microencapsulation is a commonly used technique for immunoprotection of engrafted therapeutic cells. We investigated a library of capsule formulations to determine the most optimal formulation for pancreatic beta islet cell transplantation, using barium as the gelating ion and clinical-grade protamine sulfate (PS) as a new cationic capsule cross-linker. Barium-gelated alginate/PS/alginate microcapsules (APSA, diameter聽=聽444聽卤聽21聽渭m) proved to be mechanically stronger and supported a higher cell viability as compared to conventional alginate/poly-l-lysine/alginate (APLLA) capsules. Human pancreatic islets encapsulated inside APSA capsules, gelated with 20聽mm barium as optimal concentration, exhibited a sustained morphological integrity, viability, and functionality for at least 3-4 weeks in聽vitro, with secreted human C-peptide levels of 0.2-160聽pg/ml/islet. Unlike APLLA capsules that are gelled with calcium, barium-APSA capsules are intrinsically radiopaque and, when engrafted into mice, could be readily imaged in聽vivo with micro-computed tomography (CT). Without the need of adding contrast agents, these capsules offer a clinically applicable alternative for simultaneous immunoprotection and real-time, non-invasive X-ray/CT monitoring of engrafted cells during and after in聽vivo administration.