Fluorocapsules allow in vivo monitoring of the mechanical stability of encapsulated islet cell transplants

Abstract

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 19F MRI, into dual-alginate layer, Ba2+-gelled alginate microcapsules. Fluorocapsules were spherical with an apparent smooth surface and an average diameter of 428 ± 52 μm. After transplantation into mice, the 19F 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 19F MRI signal dissipated within 4 days. For fluoroencapsulated luciferase-expressing mouse βTC6 insulinoma cells implanted into autoimmune NOD/ShiLtJ mice and subjected to alginate-lyase induced capsule rupture in vivo, the 19F 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 19F MRI signal may serve as a predictive imaging surrogate biomarker for impending failure of encapsulated islet cell therapy.