Mixed serum-deprived and normal adipose-derived mesenchymal stem cells against acute lung ischemia-reperfusion injury in rats

Background: This study hypothesized that combined serum-deprived (Sd) and healthy (He) adipose-de-rived mesenchymal stem cell (ADMSC) therapy is superior to either alone in reducing acute lung ischemia-reperfu-sion 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 × 10⁶ 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 × 10⁶ 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 oppo-site 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.