Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative
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RESEARCH
Open Access
Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction Yen-Ta Chen1†, Cheuk-Kwan Sun2,10, Yu-Chun Lin3,4†, Li-Teh Chang5, Yung-Lung Chen3, Tzu-Hsien Tsai3, Sheng-Ying Chung3, Sarah Chua3, Ying-Hsien Kao6, Chia-Hong Yen7, Pei-Lin Shao8, Kuan-Cheng Chang9, Steve Leu3,4† and Hon-Kan Yip3,4*†
Abstract Background: Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR) injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury. Methods: Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus immediate intra-renal administration of 1.0 × 106 autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR). The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed. Results: Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p < 0.03). The mRNA expressions of inflammatory, oxidative stress, and apoptotic biomarkers were lower, whereas the anti-inflammatory, anti-oxidative, and anti-apoptotic biomarkers were higher in group 3 than in group 2 (all p < 0.03). Immunofluorescent staining showed a higher number of CD31+, von Willebrand Factor+, and heme oxygenase (HO)-1+ cells in group 3 than in group 2 (all p < 0.05). Western blot showed notably higher NAD(P)H quinone oxidoreductase 1 and HO-1 activities, two indicators of anti-oxidative capacity, in group 3 than those in group 2 (all p < 0.04). Immunohistochemical staining showed higher glutathione peroxidase and glutathione reductase activities in group 3 than in group 2 (all p < 0.02) Conclusion: ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.
Background Not only is ischemia-reperfusion (IR) injury of the kidney encountered in patients with contrast mediainduced nephropathy [1] and in those with shock followed by resuscitation in the emergency and intensive care settings [2], but it is also a common early event in kidney transplantation that contributes to organ * Correspondence: [email protected] † Contributed equally 3 Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital - Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Full list of author information is available at the end of the article
dysfunction [3]. The manifestations include acute tubular-epithelial damage [4,5], loss of peri-tubular microvasculature [6], as well as inflammation and leukocyte infiltration [3-5,7]. Despite current advances in medical treatment, IR injury of the kidney, which is a common
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