Abstract
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.
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References
Zhang Z, Liao Z, Jin J, Ajani J, Chang JY, Jeter M et al. Dose-response relationship in locoregional control for patients with stage II–III esophageal cancer treated with concurrent chemotherapy and radiotherapy. IJROBP 2005; 61: 656–664.
Ahn SJ, Kahn D, Zhou S, Yu X, Hollis D, Shafman TD et al. Dosimetric and clinical predictors for radiation-induced esophageal injury. IJROBP 2005; 61: 335–347.
Socinski MA, Rosenman JG, Schell MJ, Halle J, Russo S, Rivera MP et al. Dose-escalating conformal thoracic radiation therapy with induction and concurrent carboplatin/paclitaxel in unresectable stage IIIA/B nonsmall cell lung carcinoma. A modified phase I/II trial. Cancer 2001; 92: 1213–1223.
Rosenman JG, Halle JS, Socinski MA, Deschesne K, Moore DT, Johnson H et al. High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small cell lung cancer: technical issues and results of a phase I/II trial. Int J Radiation Oncology Biol Phys 2002; 54: 348–356.
Stickle RL, Epperly MW, Klein E, Bray JA, Greenberger JS . Prevention of irradiation-induced esophagitis by plasmid/liposome delivery of the human manganese superoxide dismutase transgene. Radiat Oncol Investig 1999; 7: 204–217.
Epperly MW, Gretton JA, DeFilippi SJ, Sikora CA, Liggitt D, Koe G et al. Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmid/liposome (SOD-PL) gene therapy. Radiat Res 2001; 155: 2–14.
Epperly MW, Kagan VE, Sikora CA, Gretton JE, Defilippi SJ, Bar-Sagi D et al. Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated irradiation. Int J Cancer (Radiat Oncol Invest) 2001; 96: 221–231.
Epperly MW, Guo HL, Shen H, Niu YY, Zhang X, Jefferson M et al. Bone marrow origin of cells with capacity for homing and differentiation to esophageal squamous epithelium. Radiat Res 2004; 162: 233–240.
Epperly MW, Zhang X, Nie S, Cao S, Kagan V, Tyurin V et al. MnSOD-plasmid liposome gene therapy effects on ionizing irradiation induced lipid peroxidation of the esophagus. In vivo 2005; 19: 997–1004.
Epperly MW, Shen H, Zhang X, Nie S, Cao S, Greenberger JS . Protection of esophageal stem cells from ionizing irradiation by MnSOD-plasmid liposome gene therapy. In vivo 2005; 19: 965–974.
Epperly MW, Shen H, Jefferson M, Greenberger JS . In vitro differentiation capacity of esophageal progenitor cells with capacity for homing and repopulation of the ionizing irradiation damaged esophagus. In vivo 2004; 18: 675–685.
Epperly MW, Sikora C, Defilippi S, Gretton JA, Zhan Q, Kufe DW et al. Manganese superoxide dismutase (SOD2) inhibits radiation-induced apoptosis by stabilization of the mitochondrial membrane. Radiation Res 2002; 157: 568–577.
Epperly MW, Gretton JE, Bernarding M, Nie S, Rasul B, Greenberger JS . Mitochondrial localization of copper/zinc superoxide dismutase (Cu/ZnSOD) confers radioprotective functions in vitro and in vivo. Radiation Res 2003; 160: 568–578.
Prigozhina TB, Gurevitch O, Slavin S . Nonmyeloablative conditioning to induce bilateral tolerance after allogeneic bone marrow transplantation in mice. Exp Hematol 1999; 27: 1503–1510.
Blomberg M, Rao S, Reilly J, Tiarks C, Peters S, Kittler E et al. Repetitive bone marrow transplantation in nonmyeloablated recipients. Exp Hematol 1998; 26: 320–324.
Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 2001; 107: 1395–1402.
Krause D, Theise N, Collector M, Henegariu O, Hwang S, Gardner R et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001; 105: 369–377.
Terry NH, Travis EL . The influence of bone marrow depletion on intestinal radiation damage. Int J Radiat Oncol Biol Phys 1989; 17: 569–573.
Gorbunov NV, Pogue-Geile KL, Epperly MW, Bigbee WL, Draviam R, Day BW et al. Activation of the nitric oxide synthase 2 pathway in the response of bone marrow stromal cells to high doses of ionizing radiation. Radiat Res 2000; 154: 73–86.
Mothersill C, Seymour CB . Radiation-induced bystander effects—implications for cancer. Nat Rev Cancer 2004; 4: 158–164.
Harrison DE, Astle CM . Loss of stem cell repopulating ability upon transplantation: effects of donor age, cell number, and transplantation procedure. J Exp Med 1982; 156: 1767–1779.
Harrison DE, Astle CM, Delaittre JA . Loss of proliferative capacity immunohematopoietic stem cells caused by serial transplantation rather than aging. J Exp Med 1978; 147: 1526–1531.
Zipori D . The nature of stem cells: state rather than entity. Nat Rev 2004; 5: 873–883.
Carpenter M, Epperly MW, Agarwal A, Nie S, Hricisak L, Niu Y et al. Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage. Gene Therapy 2005; 12: 685–693.
Guo HL, Seixas-Silva JA, Epperly MW, Gretton JE, Shin DM, Greenberger JS . Prevention of irradiation-induced oral cavity mucositis by plasmid/liposome delivery of the human manganese superoxide dismutase (MnSOD) transgene. Radiat Res 2003; 159: 361–370.
Epperly MW, Carpenter M, Agarwal A, Mitra P, Nie S, Greenberger JS . Intra-oral manganese superoxide dismutase plasmid liposome radioprotective gene therapy decreases ionizing irradiation-induced murine mucosal cell cycling and apoptosis. In vivo 2004; 18: 401–410.
Friedrich G, Soriano P . Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. Genes Dev 1991; 5: 1513–1523.
Menon SG, Goswami PC . A redox cycle within the cell cycle: ring in the old with the new. Oncogene 2007; 26: 1101–1109.
Ogle BM, Cascalho M, Platt JL . Biological implications of cell fusion. Mol Cell Biol 2005; 6: 567.
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Supported by NIH Grant No CA083876.
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Niu, Y., Epperly, M., Shen, H. et al. Intraesophageal MnSOD-plasmid liposome enhances engraftment and self-renewal of bone marrow derived progenitors of esophageal squamous epithelium. Gene Ther 15, 347–356 (2008). https://doi.org/10.1038/sj.gt.3303089
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DOI: https://doi.org/10.1038/sj.gt.3303089
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