Protection of Pancreatic Islets Using Theranostic Silencing Nanoparticles in a Baboon Model of Islet Transplantation.

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 Tx efficacy. In this project, we demonstrate a novel approach aimed at protecting islets before T...

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Publicado en:Diabetes Vol. 69; no. 11; pp. 2414 - 2423
Autores principales: Pomposelli, Thomas, Wang, Ping, Takeuchi, Kazuhiro, Miyake, Katsunori, Ariyoshi, Yuichi, Watanabe, Hironosuke, Chen, Xiaojuan, Shimizu, Akira, Robertson, Neil, Yamada, Kazuhiko, Moore, Anna, Xiaojuan, Chen
Formato: diagnostic images pictorial research tables/charts Journal Article
Publicado: American Diabetes Association Nov2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Nov2020
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      pub: American Diabetes Association
      place: Arlington, Virginia
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        atl: Protection of Pancreatic Islets Using Theranostic Silencing Nanoparticles in a Baboon Model of Islet Transplantation.
      aug:
        au:
          Pomposelli, Thomas
          Wang, Ping
          Takeuchi, Kazuhiro
          Miyake, Katsunori
          Ariyoshi, Yuichi
          Watanabe, Hironosuke
          Chen, Xiaojuan
          Shimizu, Akira
          Robertson, Neil
          Yamada, Kazuhiko
          Moore, Anna
          Xiaojuan, Chen
        affil: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY
      sug:
        subj:
          Genes
          Nanoparticles
          Islets of Langerhans Transplantation
          Primates
          Animal Studies
          Islets of Langerhans Metabolism
          Funding Source
      ab: 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 Tx efficacy. In this project, we demonstrate a novel approach aimed at protecting islets before Tx in nonhuman primates (NHPs) (baboons) by silencing a gene (caspase-3) responsible for induction of apoptosis. This was done using siRNA (siCas-3) conjugated to magnetic nanoparticles (MNs). In addition to serving as carriers for siCas-3, these nanoparticles also act as reporters for MRI, so islets labeled with MN-siCas-3 can be monitored in vivo after Tx. In vitro studies showed the antiapoptotic effect of MN-siCas-3 on islets in culture, resulting in 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 with even a marginal number of labeled islets compared with 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 cadaveric or living donors.
      pubtype: Academic Journal
      doctype:
        diagnostic images
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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