87 research outputs found
Iodine Radiolabeled Mesenchymal Stem Cell (MSC)-Exosomes and Their CD73 Enzymatic Activities
IODINE RADIOLABELLED MESENCHYMAL STEM CELL (MSC)-EXOSOMES AND THEIR CD73 ENZYMATIC ACTIVITIES Chang-Tong Yang a,b*,Ruenn Chai Laic, Sai Kiang Limc, David Chee Eng Ng a,b a Department of Nuclear Medicine and Molecular Imaging, Radiological Sciences Division, Singapore General Hospital, Outram Road, 169608 Singapore; b Duke-NUS Medical School, 8 College Road, 169857 Singapore; cInstitute of Molecular & Cell Biology, 8A Biomedical Grove #05-16 Immunos, 138648, Singapore; *[email protected] Introduction MSC-derived exosomes have shown therapeutic potential in the areas of cardiovascular, orthopaedic, ophthalmologic, immune, dermatologic diseases and radiation sickness. Efficient radioisotope-labelling of exosomes remains as a challenging process. We demonstrate iodine-131 radiolabeled exosomes using both chloramine-T and Pierce Iodination methods, and characterized I-labelled exosomes via their CD73 enzymatic activities. Experimental methodology and results Two classic radio-iodination methods have been used to label exosomes due to several advantages: relatively long half-life of I-131 (half-life 8 days) and I-124 (half-life 4.2 days, 25.6% positron emission) could enable a desired tracking kinetics of exosomes in vitro and in vivo; radiolabeling of iodine to peptides and antibodies is a well-established chemistry; the unlabeled free iodine after radio-labelling can be easily removed to reach high radiochemical purity. By using chloramine-T, the radiolabeling yield of 131I-labeled-exosomes achieved ~30-40% with a radiochemical purity > 90% after running through PD10 column purification. Using Pierce Iodination, the radiolabeling yield drops to ~15-20%, radiochemical purity achieved >90% after the same purification process. The integrity of I-labeled-exosomes is important in the reproducibility and development of exosome clinical therapeutics. No radioactive iodine was labelled to exosome for characterization of their integrity. The results showed that chloramine T radiolabeling affected the structures of I-labeled-exosomes as the CD73 enzymatic activity of I-labeled exosomes was destroyed, the particle size became much larger and caused broader exosome size distribution. While with Pierce iodination the CD73 activity drops by 50 % when compared to that of the unlabeled exosomes, and the particles kept the same size. Conclusions Using chloramine T method showed that the CD73 enzymatic activity of I-labelled exosomes was destroyed, suggesting the labeling process damaged the structure of exosomes. By comparison, using Pierce Iodination method preserved the CD73 enzymatic activity, indicating that exosomes can be radiolabeled using Pierce Iodination for in vitro and in vivo tracking and pharmacokinetic studies
Iodine Radiolabeled Mesenchymal Stem Cell (MSC)-Exosomes and Their CD73 Enzymatic Activities
IODINE RADIOLABELLED MESENCHYMAL STEM CELL (MSC)-EXOSOMES AND THEIR CD73 ENZYMATIC ACTIVITIES Chang-Tong Yang a,b*,Ruenn Chai Laic, Sai Kiang Limc, David Chee Eng Ng a,b a Department of Nuclear Medicine and Molecular Imaging, Radiological Sciences Division, Singapore General Hospital, Outram Road, 169608 Singapore; b Duke-NUS Medical School, 8 College Road, 169857 Singapore; cInstitute of Molecular & Cell Biology, 8A Biomedical Grove #05-16 Immunos, 138648, Singapore; *[email protected] Introduction MSC-derived exosomes have shown therapeutic potential in the areas of cardiovascular, orthopaedic, ophthalmologic, immune, dermatologic diseases and radiation sickness. Efficient radioisotope-labelling of exosomes remains as a challenging process. We demonstrate iodine-131 radiolabeled exosomes using both chloramine-T and Pierce Iodination methods, and characterized I-labelled exosomes via their CD73 enzymatic activities. Experimental methodology and results Two classic radio-iodination methods have been used to label exosomes due to several advantages: relatively long half-life of I-131 (half-life 8 days) and I-124 (half-life 4.2 days, 25.6% positron emission) could enable a desired tracking kinetics of exosomes in vitro and in vivo; radiolabeling of iodine to peptides and antibodies is a well-established chemistry; the unlabeled free iodine after radio-labelling can be easily removed to reach high radiochemical purity. By using chloramine-T, the radiolabeling yield of 131I-labeled-exosomes achieved ~30-40% with a radiochemical purity > 90% after running through PD10 column purification. Using Pierce Iodination, the radiolabeling yield drops to ~15-20%, radiochemical purity achieved >90% after the same purification process. The integrity of I-labeled-exosomes is important in the reproducibility and development of exosome clinical therapeutics. No radioactive iodine was labelled to exosome for characterization of their integrity. The results showed that chloramine T radiolabeling affected the structures of I-labeled-exosomes as the CD73 enzymatic activity of I-labeled exosomes was destroyed, the particle size became much larger and caused broader exosome size distribution. While with Pierce iodination the CD73 activity drops by 50 % when compared to that of the unlabeled exosomes, and the particles kept the same size. Conclusions Using chloramine T method showed that the CD73 enzymatic activity of I-labelled exosomes was destroyed, suggesting the labeling process damaged the structure of exosomes. By comparison, using Pierce Iodination method preserved the CD73 enzymatic activity, indicating that exosomes can be radiolabeled using Pierce Iodination for in vitro and in vivo tracking and pharmacokinetic studies
Lumped-parameter model of renal hemodynamics
The blood flow through a porous and distensible vessel such as a glomerular capillary is studied using a lumped-parameter model, and based on simplified Navier-Stokes’ equations to derive the governing equations in the form of second-order hyperbolic partial differential equations in pressure. Further modelling of the autoregulation of flow is performed based on a extravascular tissue-pressure model. Lumped-parameter model of a compliant, porous vescular compartment was studied through simplification of Navier-Stokes equation where hyperbolic second-order partial differential equations governing flow and pressure were derived.Master of Science (Biomedical Engineering
Facing a disruptive threat: how can a nuclear medicine service be prepared for the coronavirus outbreak 2020?
10.1007/s00259-020-04790-2EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING4771645-164
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