Sodium Iodide Symporter PET and BLI Noninvasively Reveal Mesoangioblast Survival in Dystrophic Mice

• Published in: Stem cell reports Vol. 5; no. 6; pp. 1183 - 1195
• Main Authors: Holvoet, Bryan, Quattrocelli, Mattia, Belderbos, Sarah, Pollaris, Lore, Wolfs, Esther, Gheysens, Olivier, Gijsbers, Rik, Vanoirbeek, Jeroen, Verfaillie, Catherine M., Sampaolesi, Maurilio, Deroose, Christophe M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.12.2015; Elsevier
• Subjects: Animals; Blood Vessels - cytology; Cell Line; Cell Survival; Cyclosporine - therapeutic use; Genes, Reporter; Humans; Immunosuppressive Agents - therapeutic use; Luciferases, Firefly - analysis; Luciferases, Firefly - genetics; Luminescent Measurements; Mice, Inbred C57BL; Mice, Nude; Muscle Development; Muscular Dystrophy, Animal - diagnosis; Muscular Dystrophy, Animal - pathology; Muscular Dystrophy, Animal - therapy; Optical Imaging; Positron-Emission Tomography - methods; Stem Cell Transplantation; Stem Cells - cytology; Symporters - analysis; Symporters - genetics; Transduction, Genetic
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2015.10.018

Muscular dystrophies are a heterogeneous group of myopathies, characterized by muscle weakness and degeneration, without curative treatment. Mesoangioblasts (MABs) have been proposed as a potential regenerative therapy. To improve our understanding of the in vivo behavior of MABs and the effect of different immunosuppressive therapies, like cyclosporine A or co-stimulation-adhesion blockade therapy, on cell survival noninvasive cell monitoring is required. Therefore, cells were transduced with a lentiviral vector encoding firefly luciferase (Fluc) and the human sodium iodide transporter (hNIS) to allow cell monitoring via bioluminescence imaging (BLI) and small-animal positron emission tomography (PET). Non-H2 matched mMABs were injected in the femoral artery of dystrophic mice and were clearly visible via small-animal PET and BLI. Based on noninvasive imaging data, we were able to show that co-stim was clearly superior to CsA in reducing cell rejection and this was mediated via a reduction in cytotoxic T cells and upregulation of regulatory T cells. •Longitudinal monitoring of murine mesoangioblasts with BLI and small-animal PET•Noninvasive evaluation of immune suppressant efficacy•Inhibition of co-stimulation outperformed cyclosporin•Inhibition of co-stimulation reduced cytotoxic and upregulated regulatory T cells In this article, Deroose, Holvoet, and colleagues show that it is feasible to monitor mMABs in dystrophic animal models via BLI and small-animal reporter gene PET. Based on noninvasive imaging, they concluded that co-stimulation adhesion blockade was a superior immune suppressant compared to cyclosporine A. The use of a human radionuclide reporter gene (hNIS) allows translation of cell detection into a clinical setting.