Improved islet transplantation outcome by the co-delivery of siRNAs for iNOS and 17β-estradiol using an R3V6 peptide carrier

Role of Sex Steroids in β Cell Function, Growth, and Survival

“…Silencing the inflammatory protein inducible nitric oxide synthase (iNOS) in islets is another strategy to promote the survival of transplanted islets [37]. Hwang et al used peptide micelles that co-deliver small interfering RNA (siRNA)-iNOS and E2 loaded in the hydrophobic core.…”

Transgene and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus

“…Preserved transplanted islet cells with increasing vascularizationChae et al (2005)[43] R3V6 peptide micellessiRNA-iNOS, 17b-estradiolDirect transplantationLeft kidney capsuleImproved glycemic control. Reduced apoptosis of transplanted islet cellsHwang et al (2015)[87] Magnetic iron oxide nanoparticlessiRNA-human caspase-3Direct transplantationLeft kidney capsuleDecreased apoptosis in transplanted islet cellsWang et al (2011)[88] Magnetic iron oxide nanoparticlessiRNA-β 2 microglobulinDirect transplantationLeft kidney capsuleDelayed onset of diabetes mellitus caused by immune rejectionWang et al (2012)[89] Abbreviations : GLP-1: glucagon-like peptide-1; IBMIR: instant blood-mediated inflammatory reactions; PEG: polyethylene glycol; PGA: polyglycolic acid; PET: polyethylene terephthalate; bFGF: basic fibroblast growth factor; CR1: soluble complement receptor 1; PVA: polyvinyl alcohol hydrogel; VEGF: vascular endothelial growth factor; R3V6: three arginine and six valine; siRNA: short interfering RNA; iNOS: inducible nitric oxide synthase. …”

“…Islet cells over-expressing GLP-1 or vascular endothelial growth factor were shown to preserve mass and function better compared with control islet cells when transplanted into the kidney capsule of a mouse model of diabetes mellitus [43,54]. Another study reported that inducible nitric oxide synthase-siRNA and 17b-estradiol-siRNA using the R3V6 peptide vector, which comprises three arginine and six valine and which forms self-assembled micelles in aqueous solution, transplanted into islet cells and delivered into the renal subcapsular space of a mouse model of diabetes mellitus suppressed cytokine-induced transplanted islet cell destruction, resulting in better control of blood glucose levels [87]. Human islet cells treated with magnetic iron oxide nanoparticles that entrapped caspase 3-siRNA or β 2 microglobulin-siRNA were shown to inhibit apoptosis and immune rejection, respectively, when transplanted into the renal subcapsular space of a mouse model of diabetes mellitus [88,89].…”

A Simple High Efficiency Intra-Islet Transduction Protocol Using Lentiviral Vectors

“…Furthermore, several post-transplant events, such as instant blood mediated inflammatory reaction and cytokine cascade, seriously affect the long-term functionality of islets [8-11]. Ex vivo genetic modifications of islets to enhance cell function and survival prior to transplantation have been successfully demonstrated in animal models [12, 13]. This strategy can ultimately increase islet viability and performance providing a tangible approach to improve human islet transplantation and long-term insulin independence.…”