The therapeutic effect of G-CSF-mobilized autologous stem cells on radiation pulmonary injury in mice
Huiqin Sun, Tao Wang, Xueli Pang, Yu Wang, Fengchao Wang, Jun He, Qing Zhou, Shuang Long, Xinze Ran, Yongping Su
Abstract
ObjectiveTo investigate the effects of G-CSF-mobilized autologous stem cells in the prevention of radiation pulmonary injury.
MethodsMice were divided into control group, irradiation group and treatment group. Mouse model of pulmonary fibrosis was established by exposing chest to a single dose of 14 Gy. Animals in the treatment group received recombinant human G-CSF (250 μg/kg daily for 5 d) before the irradiation in order to mobilize autologous stem cells in vivo. The general condition and mortality were documented after radiation injury. The pathological study with histological scoring, Masson staining and Sirius red staining with polarized light analysis were used to identify lung injury and the potential benefit of stem cell mobilization.
ResultsLocal chest irradiation of a single dose of 14 Gy was a suitable dose to create radiation-induced pulmonary fibrosis in mice. The death rate was 37.5%, which mainly happened around 11 weeks after injury. In contrast, all of the animals in G-CSF treated group survived. The ratio of lung to body mass was significantly increased in both irradiation group and treatment group (F=23.20, P<0.05) around 3 months after the injury, with a higher ratio in irradiation group than that in treatment group (P<0.05). Histological scoring for alveolar inflammation at 3 months after injury revealed statistically significant difference in irradiation group and treatment group compared with control group (F=11.93, P<0.05). At this time point, the pathological observation showed lung tissue degeneration and necrosis with alveolitis and interstitial inflammation, as well as fibroblasts proliferation and focal collagen deposition in alveolar septa. At 4 month after the injury, the inflammation in interstitial tissue was receded, but fibrosis and collagen deposition were significantly increased. In addition, at 3 and 4 months after injury, the pulmonary fibrosis was aggravated in irradiation group(F=28.73, 16.85, P<0.05), and significantly alleviated in the treatment group (P<0.05). The similar results were confirmed in collagen content analysis (IOD) by Sirius red staining and image analysis (F=17.70, 17.79, P<0.05).
ConclusionsAutologous mobilization of stem cells could prevent the death of radiation-injured animals possibly by alleviating early lung injury and interstitial inflammation as well as the late pulmonary fibrosis, suggesting a therapeutic potential of autologous stem cell mobilization in radiation pulmonary fibrosis.
Key words:
Radiation-induced lung injury; G-CSF; Autologous stem cell mobilization; Therapeutic effect; Mice
Contributor Information
Huiqin Sun
Institute of Combined Injury, State Key laboratory of Trauma, Burn and Combined Injury, College of Military Preventive Medicine, Department of Radiation Medicie, Chongqing 400038, China
Tao Wang
Institute of Combined Injury, State Key laboratory of Trauma, Burn and Combined Injury, College of Military Preventive Medicine, Department of Radiation Medicie, Chongqing 400038, China
Xueli Pang
Department of Radiation Oncology, Southwest Hospital, Army Medical University, Chongqing 400038, China
Yu Wang
Institute of Combined Injury, State Key laboratory of Trauma, Burn and Combined Injury, College of Military Preventive Medicine, Department of Radiation Medicie, Chongqing 400038, China
Fengchao Wang
Institute of Combined Injury, State Key laboratory of Trauma, Burn and Combined Injury, College of Military Preventive Medicine, Department of Radiation Medicie, Chongqing 400038, China
Jun He
Institute of Combined Injury, State Key laboratory of Trauma, Burn and Combined Injury, College of Military Preventive Medicine, Department of Radiation Medicie, Chongqing 400038, China
Qing Zhou
Institute of Combined Injury, State Key laboratory of Trauma, Burn and Combined Injury, College of Military Preventive Medicine, Department of Radiation Medicie, Chongqing 400038, China
Shuang Long
Institute of Combined Injury, State Key laboratory of Trauma, Burn and Combined Injury, College of Military Preventive Medicine, Department of Radiation Medicie, Chongqing 400038, China
Xinze Ran
Institute of Combined Injury, State Key laboratory of Trauma, Burn and Combined Injury, College of Military Preventive Medicine, Department of Radiation Medicie, Chongqing 400038, China
Yongping Su
Institute of Combined Injury, State Key laboratory of Trauma, Burn and Combined Injury, College of Military Preventive Medicine, Department of Radiation Medicie, Chongqing 400038, China
