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dc.contributor.authorWang, Ping
dc.contributor.authorYigit, Mehmet V
dc.contributor.authorMedarova, Zdravka Ognyanova
dc.contributor.authorWei, Lingling
dc.contributor.authorDai, Guangping
dc.contributor.authorSchuetz, Christian
dc.contributor.authorMoore, Anna V.
dc.date.accessioned2012-03-28T20:01:19Z
dc.date.issued2011
dc.identifier.citationWang, Ping, Mehmet V. Yigit, Zdravka Medarova, Lingling Wei, Guangping Dai, Christian Schuetz, and Anna Moore. 2011. Combined small interfering RNA therapy and in vivo magnetic resonance imaging in islet transplantation. Diabetes 60(2): 565-571.en_US
dc.identifier.issn0012-1797en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8461890
dc.description.abstractOBJECTIVE Recent advances in human islet transplantation are hampered by significant graft loss shortly after transplantation and inability to follow islet fate directly. Both issues were addressed by utilizing a dual-purpose therapy/imaging small interfering RNA (siRNA)-nanoparticle probe targeting apoptotic-related gene caspase-3. We expect that treatment with the probe would result in significantly better survival of transplanted islets, which could be monitored by in vivo magnetic resonance imaging (MRI). RESEARCH DESIGN AND METHODS We synthesized a probe consisting of therapeutic (siRNA to human caspase-3) and imaging (magnetic iron oxide nanoparticles, MN) moieties. In vitro testing of the probe included serum starvation of the islets followed by treatment with the probe. Caspase-3 gene silencing and protein expression were determined by RT-PCR and Western blot, respectively. In vivo studies included serial MRI of NOD-SCID mice transplanted with MN-small interfering (si)Caspase-3–labeled human islets under the left kidney capsule and MN-treated islets under the right kidney capsule. RESULTS Treatment with MN-siCaspase-3 probe resulted in decrease of mRNA and protein expression in serum-starved islets compared with controls. In vivo MRI showed that there were significant differences in the relative volume change between MN-siCaspase-3–treated grafts and MN-labeled grafts. Histology revealed decreased caspase-3 expression and cell apoptosis in MN-siCaspase-3–treated grafts compared with the control side. CONCLUSIONS Our data show the feasibility of combining siRNA therapy and in vivo monitoring of transplanted islets in mice. We observed a protective effect of MN-siCaspase-3 in treated islets both in vitro and in vivo. This study could potentially aid in increasing the success of clinical islet transplantation.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Diabetes Associationen_US
dc.relation.isversionofdoi:10.2337/db10-1400en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028356/pdf/en_US
dash.licenseLAA
dc.titleCombined Small Interfering RNA Therapy and In Vivo Magnetic Resonance Imaging in Islet Transplantationen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalDiabetesen_US
dash.depositing.authorWang, Ping
dc.date.available2012-03-28T20:01:19Z
dc.identifier.doi10.2337/db10-1400*
dash.contributor.affiliatedMedarova, Zdravka
dash.contributor.affiliatedSchuetz, Christian
dash.contributor.affiliatedYigit, Mehmet V
dash.contributor.affiliatedMoore, Anna
dash.contributor.affiliatedWang, Ping
dash.contributor.affiliatedDai, Guangping


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