Protection of Pancreatic Islets Using Theranostic Silencing Nanoparticles in a Baboon Model of Islet Transplantation.
Protection of Pancreatic Islets Using Theranostic Silencing Nanoparticles in a Baboon Model of Islet Transplantation.
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作者：
Pomposelli T;Wang P;Takeuchi K;Miyake K;Ariyoshi Y;Watanabe H;Chen X;Shimizu A;Robertson N;Yamada K;Moore A
胰岛移植（Tx）作为治疗1型糖尿病的长期成功仍然有限。Tx后与细胞凋亡、炎症和其他因素相关的胰岛损失继续限制Tx功效。在这个项目中，我们展示了一种新的方法，旨在通过沉默负责诱导细胞凋亡的基因（caspase-3）来保护非人灵长类动物（NHP）（狒狒）中Tx前的胰岛。这是使用与磁性纳米颗粒（MN）缀合的siRNA（siCas-3）完成的。除了作为siCas-3的载体外，这些纳米颗粒还作为MRI的报告物，因此可以在Tx后体内监测用MN-siCas-3标记的胰岛。体外研究显示MN-siCas-3对培养物中的胰岛的抗凋亡作用，导致最小的胰岛损失。对于体内研究，供体狒狒胰岛用MN-siCas-3标记并输注到受体糖尿病受试者中。与对照组相比，在移植了少量标记胰岛的动物中观察到胰岛素需求量的显著减少。通过证明MN-siCas-3在具有挑战性的NHP模型中的保护作用，本研究提出了一种新的策略，以最大限度地减少尸体或活体供体所需的供体胰岛数量。
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.
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影响因子：
7.7
作者：
Emamaullee, Juliet A.;Shapiro, A. M. James
通讯作者：
Shapiro, A. M. James
影响因子：
7.7
作者：
Davalli, AM;Scaglia, L;Weir, GC
通讯作者：
Weir, GC
影响因子：
8.2
作者：
Gibly, R. F.;Graham, J. G.;Luo, X.;Lowe, W. L., Jr.;Hering, B. J.;Shea, L. D.
通讯作者：
Shea, L. D.
影响因子：
7.2
作者：
Helman, Aharon;Melton, Douglas A
通讯作者：
Melton, Douglas A
DOI：
10.1111/ajt.15275
发表时间：
2019-02-01
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Kandaswamy, R;Stock, P G;Kasiske, B L
通讯作者：
Kasiske, B L