Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1183-1195 |
Number of pages | 13 |
Journal | Stem cell reports |
Volume | 5 |
Issue number | 6 |
DOIs | |
State | Published - Dec 8 2015 |
Funding
The authors thank A. Van Santvoort and T. Buelens for their help in data acquisition and processing and H. Grosemans for her help in maintaining the animal colonies and molecular analyses. The radiopharmacy team from the Nuclear Medicine Department at UZ Leuven is acknowledged for 99m TcO 4 − tracer preparations. B.H. is the recipient of a research grant from the IWT-Vlaanderen. O.G. is a senior clinical investigator of the Fund for Scientific Research Flanders (1831812N). The M.S. Laboratory is supported by the Opening the Future Campaign EJJ-OPTFUT-02010 and FWO (#G060612N, #G0A8813N, and #G088715N). M.S. and C.M.V. would also like to thank Rondoufonds voor Duchenne Onderzoek for the kind donation. The C.M.V. Laboratory is supported by SBO-BRAINSTEM (#60838). We also acknowledge infrastructural funding by the InfraMouse Grant from the Hercules Foundation (ZW09-03).
ASJC Scopus subject areas
- Genetics
- Biochemistry
- Cell Biology
- Developmental Biology