Intraesophageal MnSOD-plasmid liposome enhances engraftment and self-renewal of bone marrow derived progenitors of esophageal squamous epithelium

Gene Ther. 2008 Mar;15(5):347-56. doi: 10.1038/ Epub 2007 Dec 20.


We evaluated whether the improved esophageal radiation tolerance following Manganese Superoxide Dismutase (MnSOD)-Plasmid Liposomes was explained by improved engraftment of bone marrow-derived progenitors. C57BL/6NHsd female mice pretreated with intraesophageal MnSOD-PL were irradiated to 29 Gy to the esophagus and intravenously transplanted with marrow from male B6. 129S7-Gt (ROSA) 26S OR/J ROSA (Lac-Z+, G418-resistant) mice. After 14 days, esophagi were removed and side population and non-side population cells evaluated for donor multilineage (endothelin/vimentin/F480) positive esophageal cells. Serial intravenous transplantability was tested in second generation 29 Gy esophagus-irradiated mice. Esophagi from recipients receiving swallowed MnSOD-PL 24 h prior to irradiation demonstrated significantly increased esophageal repopulation with donor bone marrow-derived Lac-Z+, G418+, Y-probe+ multilineage cells (37.8+/-1.8>50 cell Lac-Z+ foci per esophagus) compared to irradiated controls (19.8+/-1.8) P<0.0001. Serial transfer to second-generation irradiated C57BL/6NHsd mice of intravenously injected SP or NSP first generation recipient esophagus cells was also significantly enhanced by MnSOD-PL intraesophageal pretreatment (74.4+/-3.6 SP-derived Lac-Z+ foci per esophagus, 48.6+/-5.4 NSP-derived) compared to irradiation controls (23.4+/-1.8 SP, 6.0+/-3.0 NSP), P<0.0001. Thus, intraesophageal MnSOD-PL administration enhances engraftment of marrow-derived progenitors.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Combined Modality Therapy
  • Esophagus / injuries*
  • Esophagus / metabolism
  • Esophagus / pathology
  • Female
  • Gene Expression
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics
  • Hematopoietic Stem Cell Transplantation / methods*
  • In Situ Hybridization
  • Lac Operon
  • Liposomes / administration & dosage
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plasmids
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / pathology
  • Radiation Injuries, Experimental / therapy*
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism
  • Wound Healing
  • Y Chromosome


  • Liposomes
  • Superoxide Dismutase