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Abstract: PO0885

Development of Noninvasive Clinically Applicable In Vivo Tracking of Extracellular Vesicles Using Magnetic Resonance Imaging (MRI)

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Sedrakyan, Sargis, Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Akers, Johnny C., Visicell Medical Inc, San Diego, California, United States
  • Aguiari, Paola, Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Soloyan, Hasmik, Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Mkhitaryan, Seda, Visicell Medical Inc, San Diego, California, United States
  • Karapetyan, Gevorg, Children's Hospital of Los Angeles, Los Angeles, California, United States
  • De Filippo, Roger E., Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Thu, Mya S., Visicell Medical Inc, San Diego, California, United States
  • Perin, Laura, Children's Hospital of Los Angeles, Los Angeles, California, United States
Background

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.

Conclusion

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.

Funding

  • Private Foundation Support