Trimodal Gadolinium-Gold Microcapsules Containing Pancreatic Islet Cells Restore Normoglycemia in Diabetic Mice and Can Be Tracked by Using US, CT, and Positive-Contrast MR Imaging

Authors:
  • CLChristopher M. Long
    Christopher M. Long
  • AGAssaf A. Gilad
    Assaf A. Gilad
  • CAChristophe Alric
    Christophe Alric
  • SRStéphane Roux
    Stéphane Roux
  • OTOlivier Tillement
    Olivier Tillement
  • TLThomas W. Link
    Thomas W. Link
  • AAAravind Arepally
    Aravind Arepally
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Abstract
Alginate-protamine sulfate-alginate–gadolinium-gold capsules were detectable in vivo with MR, CT, and US imaging, enabling a versatile means of noninvasively monitoring engrafted capsules in real time. PurposeTo develop microcapsules that immunoprotect pancreatic islet cells for treatment of type I diabetes and enable multimodal cellular imaging of transplanted islet cells.Materials and MethodsAll 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-l-lysine–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 Ma...

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