Protection of Esophageal Multi-lineage Progenitors of Squamous Epithelium (Stem Cells) from Ionizing Irradiation by Manganese Superoxide Dismutase-Plasmid/Liposome (MnSOD-PL) Gene Therapy

Abstract

Background: Intraesophageal manganese superoxide dismutase plasmid liposome (MnSOD-PL) gene therapy protects against irradiation damage. Materials and Methods: To determine whether esophageal side population (SP) stem cells were protected, epitope-tagged (hemagglutinin) (HA) MnSOD-PL was administered to C57BL/6J mice 24 hours prior to 30 Gy esophageal irradiation. SP cells were isolated, and apoptosis and multi-lineage vimentin/endothelin/F4/80 (macrophage) colonies in vitro were quantitated. Results: The number and percent of SP cells, apoptotic cells, or numbers of multi-lineage vimentin/endothelin/F4/80-positive in vitro colonies isolated from non-irradiated HA-MnSOD-PL-treated or 30 Gyirradiated esophagus did not differ between groups. Irradiation in vitro significantly increased apoptosis in explanted non-SP cells from control (p=0.021) compared to MnSOD-PL-treated mice. Irradiation-induced cell division was significantly increased in SP cells from control-irradiated mice (p=0.001), but not MnSOD-PL-treated mice. Irradiation-induced apoptosis detected in vivo at 5 days was decreased by MnSOD-PL. Conclusion: MnSOD-PL gene therapy protects esophageal SP cells from irradiation in vitro and in vivo.