Cheuk-Kwan Sun1, Steve Leu2, Shu-Yuan Hsu3, Yen-Yi Zhen4, Li-Teh Chang5, Ching-Yen Tsai6, Yung-Lung Chen4, Yen-Ta Chen7, Tzu-Hsien Tsai4, Fan-Yen Lee8, Jiunn-Jye Sheu8, Hsueh-Wen Chang9, Hon-Kan Yip10. 1. Department of Emergency Medicine, E-Da Hospital, I-Shou University Kaohsiung, Taiwan. 2. Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan. 3. Department of Anatomy, Graduate Institute of Biomedical Sciences, Chang Gung University Medical College Taoyuan, Taiwan. 4. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan. 5. Basic Science, Department of Nursing, Meiho University Pingtung, Taiwan. 6. Institute of Molecular Biology, Academia Sinica Taipei, Taiwan. 7. Division of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan. 8. Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan. 9. Department of Biological Sciences, National Sun Yat-Sen University Kaohsiung, Taiwan. 10. Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan ; Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan ; Institute of Shock Wave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
Abstract
BACKGROUND: This study hypothesized that combined serum-deprived (Sd) and healthy (He) adipose-derived mesenchymal stem cell (ADMSC) therapy is superior to either alone in reducing acute lung ischemia-reperfusion injury (ALIRI). METHODS: Adult male Sprague-Dawley (SD) rats (n = 30) were equally randomized into group 1 (sham control), group 2 (ALIRI + culture medium), group 3 (ALIRI + intravenous autologous 1.2 × 10(6) He-ADMSCs at 30 minute, 6 h, and 24 h following lung ischemia/reperfusion for 45 minutes/72 hours, respectively), group 4 (ALIRI + 1.2 × 10(6) Sd-ADMSCs at identical time points after ischemia/reperfusion), and group 5 (ALIRI + 1.2 × 10(6) combined Sd-ADMSC/He-ADMSC 1:1). RESULTS: Blood oxygen saturation (%) was lowest in group 2, lower in groups 3 to 5 than in group 1, and lower in group 5 than in group 1, whereas right ventricular systolic pressure (RVSP) showed a reverse pattern among the five groups (all p < 0.001). Additionally, changes in histological scoring of lung parenchymal damage, inflammatory and apoptotic biomarkers showed identical pattern compared to that of RVSP in all groups (all p < 0.001). Protein expressions of VCAM-1, ICAM-1, oxidative stress, TNF-α, nuclear factor-κB, and number of CD68 + cells were highest in group 2, higher in groups 3 to 5 than in group 1, and higher in groups 3 and 4 than in group 5, whereas NQO-1 and HO-1 activities and number of CD31 + and vWF + cells showed opposite changes compared with those of inflammatory biomarkers (all p < 0.001). CONCLUSION: Combined Sd-ADMSC/He-ADMSC therapy offered superior benefit to either option alone in minimizing rodent ALIRI through suppressing oxidative stress and inflammatory reaction.
BACKGROUND: This study hypothesized that combined serum-deprived (Sd) and healthy (He) adipose-derived mesenchymal stem cell (ADMSC) therapy is superior to either alone in reducing acute lung ischemia-reperfusion injury (ALIRI). METHODS: Adult male Sprague-Dawley (SD) rats (n = 30) were equally randomized into group 1 (sham control), group 2 (ALIRI + culture medium), group 3 (ALIRI + intravenous autologous 1.2 × 10(6) He-ADMSCs at 30 minute, 6 h, and 24 h following lung ischemia/reperfusion for 45 minutes/72 hours, respectively), group 4 (ALIRI + 1.2 × 10(6) Sd-ADMSCs at identical time points after ischemia/reperfusion), and group 5 (ALIRI + 1.2 × 10(6) combined Sd-ADMSC/He-ADMSC 1:1). RESULTS: Blood oxygen saturation (%) was lowest in group 2, lower in groups 3 to 5 than in group 1, and lower in group 5 than in group 1, whereas right ventricular systolic pressure (RVSP) showed a reverse pattern among the five groups (all p < 0.001). Additionally, changes in histological scoring of lung parenchymal damage, inflammatory and apoptotic biomarkers showed identical pattern compared to that of RVSP in all groups (all p < 0.001). Protein expressions of VCAM-1, ICAM-1, oxidative stress, TNF-α, nuclear factor-κB, and number of CD68 + cells were highest in group 2, higher in groups 3 to 5 than in group 1, and higher in groups 3 and 4 than in group 5, whereas NQO-1 and HO-1 activities and number of CD31 + and vWF + cells showed opposite changes compared with those of inflammatory biomarkers (all p < 0.001). CONCLUSION: Combined Sd-ADMSC/He-ADMSC therapy offered superior benefit to either option alone in minimizing rodent ALIRI through suppressing oxidative stress and inflammatory reaction.
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