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

被引：193

作者：

Lin, Kun-Chen ^{[1
,2
]}

Yip, Hon-Kan ^{[2
,3
,4
,5
,6
,7
]}

Shao, Pei-Lin ^{[7
]}

Wu, Shun-Cheng ^{[8
]}

Chen, Kuan-Hung ^{[1
,2
]}

Chen, Yen-Ta ^{[2
,9
]}

Yang, Chih-Chao ^{[2
,10
]}

Sun, Cheuk-Kwan ^{[11
]}

Kao, Gour-Shenq ^{[2
,3
]}

Chen, Sheng-Yi ^{[2
,3
]}

Chai, Han-Tan ^{[2
,3
]}

Chang, Chia-Lo ^{[2
,12
]}

Chen, Chih-Hung ^{[2
,13
]}

Lee, Mel S. ^{[2
,14
]}

机构：

[1] Kaohsiung Chang Gung Mem Hosp, Dept Anesthesiol, Kaohsiung 83301, Taiwan

[2] Chang Gung Univ, Coll Med, Kaohsiung 83301, Taiwan

[3] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Cardiol, Kaohsiung 83301, Taiwan

[4] Kaohsiung Chang Gung Mem Hosp, Inst Translat Res Biomed, Kaohsiung 83301, Taiwan

[5] Kaohsiung Chang Gung Mem Hosp, Ctr Shockwave Med & Tissue Engn, Kaohsiung 83301, Taiwan

[6] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan

[7] Asia Univ, Dept Nursing, Taichung 41354, Taiwan

[8] Kaohsiung Med Univ, Orthopaed Res Ctr, Kaohsiung, Taiwan

[9] Kaohsiung Chang Gung Mem Hosp, Dept Surg, Div Urol, Kaohsiung 83301, Taiwan

[10] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Nephrol, Kaohsiung 83301, Taiwan

[11] I Shou Univ, Sch Med Int Students, Dept Emergency Med, E Da Hosp, Kaohsiung 82445, Taiwan

[12] Kaohsiung Chang Gung Mem Hosp, Dept Surg, Div Colorectal Surg, Kaohsiung 83301, Taiwan

[13] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Gen Med, Kaohsiung 83301, Taiwan

[14] Kaohsiung Chang Gung Mem Hosp, Dept Orthoped, Kaohsiung 83301, Taiwan

来源：

INTERNATIONAL JOURNAL OF CARDIOLOGY | 2016年 / 216卷

关键词：

Acute kidney ischemia-reperfusion injury; Exosome; Adipose-derived mesenchymal stem cell; Inflammation; Oxidative stress; CRITICALLY-ILL PATIENTS; LEFT-VENTRICULAR FUNCTION; ACUTE-RENAL-FAILURE; OXIDATIVE STRESS; RIFLE CRITERIA; THERAPY; SEPSIS; MELATONIN; DISEASE; PROGNOSIS;

D O I：

10.1016/j.ijcard.2016.04.061

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 1 h and reperfusion for 72 h 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 (100 mu g)], group 4 [IR + ADMSC (1.2 x 10(6) cells)], and group 5 (IR-exosome-ADMSC). All therapies were performed at 3 h after IR procedure from venous administration. By 72 h, 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-alpha/NF-kappa B/IL-1 beta/MIF/PAI-1/Cox-2), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (Bax/caspase-3/PARP), and fibrotic (Smad3/TGF-beta) 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 (gamma-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. (C) 2016 Published by Elsevier Ireland Ltd.

引用

页码：173 / 185

页数：13

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