Abstract
Magnetoliposomes (MLs) were synthesized and tested for longitudinal monitoring of transplanted pancreatic islets using magnetic resonance imaging (MRI) in rat models. The rat insulinoma cell line INS-1E and isolated pancreatic islets from outbred and inbred rats were used to optimize labeling conditions in vitro. Strong MRI contrast was generated by islets exposed to 50 µg Fe/ml for 24 hours without any increased cell death, loss of function or other signs of toxicity. In vivo experiments showed that pancreatic islets (50–1000 units) labeled with MLs were detectable for up to 6 weeks post-transplantation in the kidney subcapsular space. Islets were also monitored for two weeks following transplantation through the portal vein of the liver. Hereby, islets labeled with MLs and transplanted under the left kidney capsule were able to correct hyperglycemia and had stable MRI signals until nephrectomy. Interestingly, in vivo MRI of streptozotocin induced diabetic rats transplanted with allogeneic islets demonstrated loss of MRI contrast between 7–16 days, indicative of loss of islet structure. MLs used in this study were not only beneficial for monitoring the location of transplanted islets in vivo with high sensitivity but also reported on islet integrity and hereby indirectly on islet function and rejection.
Highlights
A potential alternative treatment of T1D, in particular in patients that are inadequately regulated by insulin injection and experience severe hypoglycaemia, is the transplantation of pancreatic islets[4,5,6]
MLs were synthesized as described[33]. They were characterized by transmission electron microscopy (TEM), Dynamic Light Scattering (DLS), zeta potential and relaxivity (r1/r2) measurements
TEM indicates a spherical morphology of iron oxide particles, each individually enveloped by a phospholipid bilayer (Fig. 1)
Summary
A potential alternative treatment of T1D, in particular in patients that are inadequately regulated by insulin injection and experience severe hypoglycaemia, is the transplantation of pancreatic islets[4,5,6]. Dextran is a large macromolecule, which continually undergoes conformational changes and is even found to completely desorb from the particle surface This can rapidly result in bare iron oxide cores exposed to the degradative lysosomal environment, causing oxidative stress and loss of MRI contrast[29]. MLs consist of a phospholipid bilayer with an inner layer strongly chemisorbed onto the iron oxide core, while an outer layer is more loosely adsorbed allowing easy modifications of this outer layer transferring functionalized lipids between MLs and pre-functionalized liposomes[30] These MLs have limited toxicity, result in relatively rapid cellular uptake and allow high intracellular iron concentrations in a wide variety of cell types, including mesenchymal stem cells, immune and others[31].
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