Protection of Pancreatic Islets Using Theranostic Silencing Nanoparticles in a Baboon Model of Islet Transplantation.
Diabetes
; 69(11): 2414-2422, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32855170
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transplante das Ilhotas Pancreáticas
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Inativação Gênica
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Nanopartículas
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Medicina de Precisão
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article