Abstract 3683: MR-Guided Targeted Delivery and Imaging of Magnetocapsules Immunoprotecting Pancreatic Islet Cells
PURPOSE Islet transplantation provides a fine regulation of insulin that is unachievable by exogenous insulin injection. A means of correlating long-term function of individual islets with the anatomical location and an effective method of transplantation is desired. To this end, we have developed novel alginate-based capsules containing Feridex which provide immunoisolation and enable MR imaging of islets in vivo.
METHODS The protocol we have developed for synthesizing magnetocapsules is based upon the PLL-alginate protocol utilized for microen-capsulation. To the core layer of alginate, we have added Feridex at a concentration of 20% w/v.
RESULTS The viability and insulin secretion of magnetoencapsulated human islets were not found to differ significantly from controls. Following intraperitoneal transplantation of magnetoencapsulated murine β-cells, diabetic mice (n=15) regained normoglycemic for the observed two months, whereas non-transplanted mice (n=15) remained severely hyperglycemic. Next, magnetocapsules were transplanted via targeted intraportal infusion into the liver of swine (n=5) using a novel transvenous procedure with a MR-trackable needle (Fig 1a,b⇓); grafting throughout the entire liver was visible by a 1.5T MRI scanner (Fig 1c,d⇓). In the swine in which human islets were transplanted, Human C-peptide could be detected for the three weeks in which the animal was observed at levels ranging from 0.26 to 0.47 ng/mL.
CONCLUSION This study represents a first attempt towards transplanting encapsulated islets intraportally in a large-animal model and demonstrates that magnetocapsules are MR-trackable and maintain preserved islet function.