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.
journal_name
Diabetesjournal_title
Diabetesauthors
Pomposelli T,Wang P,Takeuchi K,Miyake K,Ariyoshi Y,Watanabe H,Chen X,Shimizu A,Robertson N,Yamada K,Moore Adoi
10.2337/db20-0517subject
Has Abstractpub_date
2020-11-01 00:00:00pages
2414-2422issue
11eissn
0012-1797issn
1939-327Xpii
db20-0517journal_volume
69pub_type
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