In type I diabetes mellitus, islet transplantation provides a moment-to-moment fine regulation of insulin. Success rates vary widely, however, necessitating suitable methods to monitor islet delivery, engraftment and survival. Here magnetic resonance-trackable magnetocapsules have been used simultaneously to immunoprotect pancreatic beta-cells and to monitor, non-invasively in real-time, hepatic delivery and engraftment by magnetic resonance imaging (MRI). Magnetocapsules were detected as single capsules with an altered magnetic resonance appearance on capsule rupture. Magnetocapsules were functional in vivo because mouse beta-cells restored normal glycemia in streptozotocin-induced diabetic mice and human islets induced sustained C-peptide levels in swine. In this large-animal model, magnetocapsules could be precisely targeted for infusion by using magnetic resonance fluoroscopy, whereas MRI facilitated monitoring of liver engraftment over time. These findings are directly applicable to ongoing improvements in islet cell transplantation for human diabetes, particularly because our magnetocapsules comprise clinically applicable materials.

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Purpose:To develop microcapsules that immunoprotect pancreatic islet cells for treatment of type I diabetes and enable multimodal cellular imaging of transplanted islet cells. Materials and Methods:All animal experiments were approved by the institutional animal care and use committee. Gold nanoparticles functionalized with DTDTPA (dithiolated diethylenetriaminepentaacetic acid):gadolinium chelates (GG) were coencapsulated with pancreatic islet cells by using protamine sulfate as a clinical-grade alginate cross linker. Conventional poly-Llysine-cross-linked microcapsules and unencapsulated islets were included as controls. The viability and glucose responsiveness of islet cells were assessed in vitro, and in vivo insulin (C-peptide) secretion was monitored for 6 weeks in (streptozotocin-induced) diabetic mice with ( n = 7) or without ( n = 8) intraabdominally engrafted islet cells. Five nondiabetic mice were included as controls. Differences between samples were calculated by using a nonparametric Wilcoxon Mann-Whitney method. To adjust for multiple comparisons, a signifi cance level of P , .01 was chosen. Generalized estimating equations were used to model cell function over time. Three mice with engrafted capsules were imaged in vivo with high-fi eld-strength (9.4-T) magnetic resonance (MR) imaging, micro-computed tomography (CT), and 40-MHz ultrasonography (US). Results:Encapsulated human pancreatic islets were functional in vitro for at least 2 weeks after encapsulation. Blood glucose levels in the diabetic mice transplanted with GG-labeled encapsulated mouse b TC6 insulinoma cells returned to normal within 1 week after transplantation, and normoglycemia was sustained for at least 6 weeks without the use of immunosuppressive drugs. GG microcapsules could be readily visualized with positive-contrast high-fi eld-strength MR imaging, micro-CT, and US both in vitro and in vivo. Conclusion:Cell encapsulation with GG provides a means of trimodal noninvasive tracking of engrafted cells.

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