Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury.

Abstract

BACKGROUND In this study, we tested the hypothesis that a combined adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy protected rat kidney from acute ischemia-reperfusion (IR) injury (i.e., ligation of both renal arteries for 1h and reperfusion for 72h prior to euthanization). METHODS AND RESULTS Adult-male SD rats (n=40) were equally categorized into group 1 (sham control), group 2 (IR), group 3 [IR+exosome (100μg)], group 4 [IR+ADMSC (1.2×10(6) cells)], and group 5 (IR-exosome-ADMSC). All therapies were performed at 3h after IR procedure from venous administration. By 72h, the creatinine level and kidney injury score were the lowest in group 1 and the highest in group 2, significantly higher in group 3 than in groups 4 and 5, and significantly higher in group 4 than in group 5 (all P<0.0001). The protein expression of inflammatory (TNF-α/NF-κB/IL-1β/MIF/PAI-1/Cox-2), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (Bax/caspase-3/PARP), and fibrotic (Smad3/TGF-β) biomarkers showed an identical pattern, whereas the anti-apoptotic (Smad1/5, BMP-2) and angiogenesis (CD31/vWF/angiopoietin) biomarkers and mitochondrial cytochrome-C showed an opposite pattern of creatinine level among the five groups (all P<0.001). The microscopic findings of glomerular-damage (WT-1), renal tubular-damage (KIM-1), DNA-damage (γ-H2AX), inflammation (MPO/MIF/CD68) exhibited an identical pattern, whereas the podocyte components (podocin/p-cadherin/synaptopodin) displayed a reversed pattern of creatinine level (all P<0.0001). CONCLUSION Combined exosome-ADMSC therapy was superior to either one for protecting kidney from acute IR injury.

DOI: 10.1016/j.ijcard.2016.04.061
05010020162017
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@article{Lin2016CombinationOA, title={Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury.}, author={Kun-Chen Lin and Hon-Kan Yip and Pei-Lin Shao and Shun-Cheng Wu and Kuan-Hung Chen and Yen-ta Chen and Chih-Chao Yang and Cheuk-Kwan Sun and G I Kao and Sheng-Yi Chen and Han-Tan Chai and Chia-Lo Chang and Chih-Hung Chen and Mel S Lee}, journal={International journal of cardiology}, year={2016}, volume={216}, pages={173-85} }