Cyanidin-3-O-Glucoside Enhanced Islet Function And MRI Of PVP-SPIO Labeled Islet

Background:Islet transplantation has been shown to be an effective treatment option for insulin-dependent diabetes mellitus, but still faces the problems of low efficiency of transplantation, lacking donorsand effective monitor tools. It was previously shown that islets are susceptible to oxidative stress due to their inherent low antioxidant capacity. Therefore, in this study, we determined whether treatment of mouse islets with an antioxidant Cyanidin-3-O-glucoside (C3G) could enhance their function after transplantation under the kidney capsule or into the portal vein. This study investigates whether self-synthesized polyvinylpyrrolidone coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) would affect the function of neonatal porcine islets (NPIs) and could be applied to monitor NPI xenograft in vivo.Methods:B6mouse islets were treated with various concentrations of C3G, their viability, and the expression of antioxidant (HO-1) and anti-apoptotic (β-catenin, Bcl-2, and Survivin) genes were determined. C3G treated (10μM) or untreated B6mouse islets (100,200, and400IEQ) were transplanted under the kidney capsule or into the portal vein of diabetic B6mice and their blood glucose levels were monitored for more than100days post-transplantation. PVP-SPIO labeled islets were transplanted under kidney capsules of immunodeficient diabetic or non-diabetic mice. Recipient mice were reconstituted by injecting splenocytes from immunocompetent mice after they recovered from diabetes. Magnetic resonance imaging (MRI) studies were performed on NPIs phantom or recipient mice after transplantation/rejection.Results:C3G treated islets showed higher cell viability compared to untreated control and the expression of HO-1; β-catenin, Bcl-2, and Survivin genes were enhanced in a concentration dependent manner. All mice that were transplanted with C3G treated islets achieved normoglycemia faster than recipients of untreated islets.Mice that received400,200or100IEQ treated islets and400or200IEQ untreated transplanted under the kidney capsule achieved normoglycemia. Only mice that were transplanted with400and200IEQ treated islets and400IEQ untreated islets into the portal vein achieved normoglycemia. Phantom of labeled NPIs could be visualized clearly by MRI. All diabetic recipient mice reach normoglycemia. The graft could be visualized as homogenous hyptointense area by MRI at2,7and more than100days post-transplantation. The graft area significantly expanded with mixed signal when rejection happened. Conclusion:Our results show that C3G could enhance the viability of mouse islets and improved their function after transplantation. PVP-SPIO did not affect the function of NPIs and the morphology and MR signal change of labeled NPIs transplanted under the kidney capsule of mice after rejection.