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

• Published in: Molecular imaging and biology Vol. 23; no. 3; pp. 361 - 371
• 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: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2021; Springer Nature B.V
• Subjects: Biodistribution; Cell therapy; Chelation; Computed tomography; Ethylenediaminetetraacetic acids; Extracellular vesicles; Feasibility studies; Imaging; In vivo methods and tests; Injection; Kidneys; Medical imaging; Medicine; Medicine & Public Health; Mesenchymal stem cells; Organs; Radiochemical analysis; Radiolabelling; Radiology; Research Article; Spleen; Stem cells; Molecular imaging; Extracellular vesicles; Wharton’s jelly MSC
• ISSN: 1536-1632; 1860-2002; 1860-2002
• DOI: 10.1007/s11307-020-01562-0

Purpose 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 111 In-labeling and μSPECT/CT imaging. Procedures 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 111 In-oxine, 111 In-EVs were injected into C57BL/6 mice followed by μSPECT/CT imaging. Organs were then taken out for ex vivo biodistribution analysis. Results The radiochemical purity of 111 In-EVs was > 90 % and remained stable up to 24 h. The image results showed that with injection of 111 In-EVs, the signal mainly accumulated in the liver, spleen, and kidney, compared to that in lung and kidney after 111 In-oxine injection. The ex vivo biodistribution showed the similar pattern to that of imaging. Chelation of free 111 In with EDTA was found necessary to reduce the nonspecific accumulation of signal. Conclusion This study demonstrated the feasibility of radiolabeling WJ-MSC-EVs with 111 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.