Protection of esophageal multi-lineage progenitors of squamous epithelium (stem cells) from ionizing irradiation by manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) gene therapy.
BACKGROUND
Intraesophageal manganese superoxide dismutase plasmid liposome (MnSOD-PL) gene therapy protects against irradiation damage.


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 Gy-irradiated 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.


CONCLUSIONS
MnSOD-PL gene therapy protects esophageal SP cells from irradiation in vitro and in vivo.
Niu
Yunyun
Y
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Shen
Hongmei
H
Epperly
Michael
M
Zhang
Xichen
X
Nie
Suhua
S
Cao
Shaonan
S
Greenberger
Joel S
JS
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis / Q000528:radiation effects; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002455:Cell Division / Q000528:radiation effects; D019070:Cell Lineage; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism; D004947:Esophagus / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D015316:Genetic Therapy; D008081:Liposomes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000473:pathology* / Q000517:prevention & control; D011835:Radiation Protection; D011839:Radiation, Ionizing; D013234:Stem Cells / Q000166:cytology / Q000528:radiation effects*; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000235:genetics; D014746:Vimentin / Q000378:metabolism
D017304:Annexin A5; D000943:Antigens, Differentiation; D015415:Biomarkers; D016232:Endothelins; D005456:Fluorescent Dyes; D008081:Liposomes; D018809:Proliferating Cell Nuclear Antigen; D014746:Vimentin; C036763:monocyte-macrophage differentiation antigen; D013482:Superoxide Dismutase; D016650:Fluorescein-5-isothiocyanate