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

Stem Cell Reports. 2015 Dec 8;5(6):1183-1195. doi: 10.1016/j.stemcr.2015.10.018. Epub 2015 Nov 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Immunosuppressive Agents
  • Symporters
  • sodium-iodide symporter
  • Cyclosporine
  • Luciferases, Firefly