Preclinical Characterization and In Vivo Imaging of 111 In-Labeled Mesenchymal Stem Cell-Derived Extracellular Vesicles

• Published in: Molecular imaging and biology 2021-06, Vol.23 (3), p.361
• Main Authors: Lu, Cheng-Hsiu, Chen, Yi-An, Ke, Chien-Chih, Chiu, Sain-Jhih, Chen, Chao-Cheng, Hsieh, Ya-Ju, Yang, Bang-Hung, Liu, Ren-Shyan
• Format: Article
• Language: English
• Subjects: Animals; Cell Lineage; Cell Proliferation; Culture Media, Conditioned; Extracellular Vesicles - metabolism; Male; Mesenchymal Stem Cells - cytology; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Nanoparticles; Organometallic Compounds - chemistry; Oxyquinoline - analogs & derivatives; Oxyquinoline - chemistry; Tissue Distribution; Tomography, Emission-Computed, Single-Photon - methods; Tomography, X-Ray Computed - methods; Wharton Jelly
• ISSN: 1860-2002
• DOI: 10.1007/s11307-020-01562-0

Mesenchymal stem cell-derived EVs (MSC-EVs) are demonstrated to have similar therapeutic effect as their cells of origin and represent an attractive cell-free stem cell therapy. With the potential to be the future medical regimen, the information of fate and behavior of MSC-EVs in the living subject should be urgently gathered. This study aimed to track MSC-EVs by In-labeling and μSPECT/CT imaging. Wharton's jelly-MSC-EVs (WJ-MSC-EVs) were isolated using Exo-Prep kit followed by characterization of expressing markers and size. After labeled by In-oxine, In-EVs were injected into C57BL/6 mice followed by μSPECT/CT imaging. Organs were then taken out for ex vivo biodistribution analysis. The radiochemical purity of In-EVs was > 90 % and remained stable up to 24 h. The image results showed that with injection of In-EVs, the signal mainly accumulated in the liver, spleen, and kidney, compared to that in lung and kidney after In-oxine injection. The ex vivo biodistribution showed the similar pattern to that of imaging. Chelation of free In with EDTA was found necessary to reduce the nonspecific accumulation of signal. This study demonstrated the feasibility of radiolabeling WJ-MSC-EVs with In-oxine for in vivo imaging and quantitative analysis in a mouse model. This simple and quick labeling method preserves the characteristics of WJ-MSC-EVs. The results in this study provide a thorough and objective basis for future clinical study.