title: Microcapsules with intrinsic barium radiopacity for immunoprotection and X-ray/CT imaging of pancreatic islet cells.
abstract: 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 = 444 ± 21 μm) 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 mm barium as optimal concentration, exhibited a sustained morphological integrity, viability, and functionality for at least 3-4 weeks in vitro, with secreted human C-peptide levels of 0.2-160 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 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 vivo administration.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Dian R
authors.initials: DR
authors.lastname: Arifin
authors.forename: Sameer
authors.initials: S
authors.lastname: Manek
authors.forename: Emma
authors.initials: E
authors.lastname: Call
authors.forename: Aravind
authors.initials: A
authors.lastname: Arepally
authors.forename: Jeff W M
authors.initials: JW
authors.lastname: Bulte
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001464:Barium / Q000737:chemistry*; D002214:Capsules / Q000737:chemistry*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000000981:diagnostic imaging*; D051379:Mice; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D000464:Alginates; D002214:Capsules; C051546:alginate-polylysine-alginate; D001464:Barium; D011107:Polylysine