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Magnetic resonance–guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells

Abstract

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 β-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 β-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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Figure 1: Macroscopic and microscopic appearance of magnetocapsules.
Figure 2: Functionality of magnetocapsule human islets is retained in vitro.
Figure 3: MRI appearance of magnetocapsules.
Figure 4: Functionality of magnetocapsule insulinoma cells in vivo in mice.
Figure 5: Magnetic resonance–guided transplantation of magnetocapsules and functionality in vivo in swine.

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Acknowledgements

A.A. Gilad and J. Ruiz-Cabello assisted with MRI, K. Schuleri with photography, and G. Clark with discussing clinical translation. Human islets were provided by the National Islet Cell Resource Center, and we thank in particular G. Weir. This work was supported by grants from the National Institutes of Health (K08 EB004348 to A.A., RO1 EB007825 to J.W.M.B., and RO1 NS045062 to J.W.M.B.). B.B. is a Howard Hughes Medical Institute Research Training Fellow and Henry Strong Denison Research Scholar.

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Correspondence to Aravind Arepally.

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Supplementary information

Supplementary Text and Figures

Supplementary Fig. 1, Supplementary Table 1, Supplementary Methods. (PDF 1741 kb)

Supplementary Movie 1

Magnetoencapsulation allows for real-time MR-guided targeted delivery. (MOV 3779 kb)

Supplementary Movie 2

Liver engraftment of MCs. (MOV 3747 kb)

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Barnett, B., Arepally, A., Karmarkar, P. et al. Magnetic resonance–guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells. Nat Med 13, 986–991 (2007). https://doi.org/10.1038/nm1581

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