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Protection of pancreatic islets using theranostic silencing nanoparticles in a baboon model of islet transplantation

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posted on 27.08.2020 by Ada Admin, Thomas Pomposelli, Ping Wang, Kazuhiro Takeuchi, Katsunori Miyake, Yuichi Ariyoshi, Hironosuke Watanabe, Xiaojuan Chen, Akira Shimizu, Neil Robertson, Kazuhiko Yamada, Anna Moore
The long-term success of pancreatic islet transplantation (Tx) as a cure for type 1 diabetes remains limited. Islet loss after Tx related to apoptosis, inflammation and other factors continues to limit its efficacy. In this project we demonstrate a novel approach aimed at protection of islets prior to Tx in non-human primates (NHP, baboons) by silencing a gene (caspase 3) responsible for induction of apoptosis. This was done using small interfering RNA (siRNA, siCas-3) conjugated to magnetic nanoparticles (MN). In addition to serving as carriers for siCas-3 these nanoparticles also act as reporters for magnetic resonance imaging so islets labeled with MN-siCas-3 can be monitored in vivo after Tx. In vitro studies showed the anti-apoptotic effect of MN-siCas-3 on islets in culture resulting in a minimal islet loss. For in vivo studies donor baboon islets were labeled with MN-siCas-3 and infused into recipient diabetic subjects. A dramatic reduction in insulin requirements was observed in animals transplanted even with a marginal number of labeled islets compared to controls. By demonstrating the protective effect of MN-siCas-3 in the challenging NHP model, this study proposes a novel strategy to minimize the number of donor islets required from either cadaver or living donor.


This work was supported in part by R01DK105503 and R01DK105468 to A.M. and K.Y.



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