MP22-16 DEVELOPMENT OF NON-INVASIVE CLINICALLY APPLICABLE IN VIVO TRACKING OF EXTRACELLULAR VESICLES USING MAGNETIC RESONANCE IMAGING (MRI)

Abstract

You have accessJournal of UrologyImaging/Radiology: Uroradiology II (MP22)1 Sep 2021MP22-16 DEVELOPMENT OF NON-INVASIVE CLINICALLY APPLICABLE IN VIVO TRACKING OF EXTRACELLULAR VESICLES USING MAGNETIC RESONANCE IMAGING (MRI) Johnny Akers, Paola Aguiari, Hasmik Soloyan, Seda Mkhitaryan, Gevorg Karaptyan, Roger De Filippo, Mya Thu, Laura Perin, and Sargis Sedrakyan Johnny AkersJohnny Akers More articles by this author , Paola AguiariPaola Aguiari More articles by this author , Hasmik SoloyanHasmik Soloyan More articles by this author , Seda MkhitaryanSeda Mkhitaryan More articles by this author , Gevorg KaraptyanGevorg Karaptyan More articles by this author , Roger De FilippoRoger De Filippo More articles by this author , Mya ThuMya Thu More articles by this author , Laura PerinLaura Perin More articles by this author , and Sargis SedrakyanSargis Sedrakyan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002013.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSC) hold great potential for the treatment of chronic kidney diseases (CKD). We have already shown that AFSC-EVs are renoprotective in a mouse model of CKD, Alport syndrome. However, there is an important unmet need for real-time in vivo monitoring of these therapeutic EVs after they are injected into a subject to understand their safety, targeting, and effectiveness. While current optical imaging solutions like bioluminescence and fluorescence are useful for EV tracking studies in animal models, there is limited utility in clinical applications. Here we present a novel in vivo tracking solution for our therapeutic EVs in Alport mice, utilizing clinically applicable MRI technology. METHODS: To generate trackable EVs, AFSC were labeled with a novel magnetic agent (VSCM). EVs secreted by the labeled AFSC were isolated by ultracentrifugation. The viability and morphology of labeled-cells were evaluated, and the in vitro MR properties of EVs were analyzed by magnetometer. Purity, potency and identity of labeled EV was compared to non-labeled EVs. In vivo biodistribution of labeled EVs was evaluated in WT and Alport mice by MRI at 10 min and 3 hr post injection, and retro-orbital and intra-cardiac routes of delivery were compared. RESULTS: The magnetic label did not affect the physiological characteristics of the cells and did not change identity, purity and potency (therapeutic effect in vivo) of EVs. MRI phantom studies confirmed the in vitro/ex vivo detectability of labeled-EVs. Importantly, as expected MRI studies showed that EV homing to the kidney injected intra-cardiacally into Alport mice was more efficient vs the retro-orbital route, and Prussian blue staining of sections confirmed EV homing to the kidney. CONCLUSIONS: We have developed a clinically applicable novel magnetic nanoparticle agent that can be used to label and track the biodistribution of EVs in the kidney and other organs using non-invasive, safe, and effective MRI technology that’s widely available. This technology is highly adaptable and can be deployed in both preclinical and clinical settings. Source of Funding: The GOFARR Fund; Research Career Development Award, TSRI, CHLA © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e397-e398 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Johnny Akers More articles by this author Paola Aguiari More articles by this author Hasmik Soloyan More articles by this author Seda Mkhitaryan More articles by this author Gevorg Karaptyan More articles by this author Roger De Filippo More articles by this author Mya Thu More articles by this author Laura Perin More articles by this author Sargis Sedrakyan More articles by this author Expand All Advertisement Loading ...