Cheng-Hsiu Lu1,2, Yi-An Chen2,3, Chien-Chih Ke4,5,6, Sain-Jhih Chiu2, Chao-Cheng Chen3, Ya-Ju Hsieh7,8,9, Bang-Hung Yang10,11, Ren-Shyan Liu12,13,14,15,16. 1. Industrial Ph.D Program of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan. 2. Molecular and Genetic Imaging Core/Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan. 3. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 4. Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan. s2289.tw@yahoo.com.tw. 5. Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. s2289.tw@yahoo.com.tw. 6. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. s2289.tw@yahoo.com.tw. 7. Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan. 8. Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. 9. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 10. National PET and Cyclotron Center (NPCC), Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 11. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. 12. Industrial Ph.D Program of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan. rsliuvgh@gmail.com. 13. Molecular and Genetic Imaging Core/Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan. rsliuvgh@gmail.com. 14. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. rsliuvgh@gmail.com. 15. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. rsliuvgh@gmail.com. 16. Department of Nuclear Medicine, Cheng Hsin Hospital, Taipei, Taiwan. rsliuvgh@gmail.com.
Abstract
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 111In-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 111In-oxine, 111In-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 111In-EVs was > 90 % and remained stable up to 24 h. The image results showed that with injection of 111In-EVs, the signal mainly accumulated in the liver, spleen, and kidney, compared to that in lung and kidney after 111In-oxine injection. The ex vivo biodistribution showed the similar pattern to that of imaging. Chelation of free 111In with EDTA was found necessary to reduce the nonspecific accumulation of signal. CONCLUSION: This study demonstrated the feasibility of radiolabeling WJ-MSC-EVs with 111In-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.
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 111In-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 111In-oxine, 111In-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 111In-EVs was > 90 % and remained stable up to 24 h. The image results showed that with injection of 111In-EVs, the signal mainly accumulated in the liver, spleen, and kidney, compared to that in lung and kidney after 111In-oxine injection. The ex vivo biodistribution showed the similar pattern to that of imaging. Chelation of free 111In with EDTA was found necessary to reduce the nonspecific accumulation of signal. CONCLUSION: This study demonstrated the feasibility of radiolabeling WJ-MSC-EVs with 111In-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.