Intraesophageal MnSOD-plasmid liposome enhances engraftment and self-renewal of bone marrow derived progenitors of esophageal squamous epithelium.
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.
Niu
Y
Y
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
Epperly
M W
MW
Shen
H
H
Smith
T
T
Wang
H
H
Greenberger
J S
JS
D000284:Administration, Oral; D000818:Animals; D003131:Combined Modality Therapy; D004947:Esophagus / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D017403:In Situ Hybridization; D007763:Lac Operon; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing; D014998:Y Chromosome
D008081:Liposomes; D013482:Superoxide Dismutase