Exendin-4-assisted Adipose Derived Mesenchymal Stem Cell Therapy Protects Renal Function Against Co-existing Acute Kidney Ischemia-reperfusion Injury and Severe Sepsis Syndrome in Rat

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2017 Aug 15

PMID 28804538

Citations 17

Authors

Pei-Hsun Sung

Hsin-Ju Chiang

Christopher Glenn Wallace

Chih-Chao Yang

Yen-Ta Chen

Kuan-Hung Chen

Chih-Hung Chen

Pei-Lin Shao

Yung-Lung Chen

Sarah Chua

Han-Tan Chai

Yi-Ling Chen

Tien-Hung Huang

Hon-Kan Yip

Mel S Lee

Affiliations

Soon will be listed here.

Abstract

This study tested the hypothesis that combined therapy with exendin-4 (Ex4) and autologous adipose-derived mesenchymal stem cells (ADMSCs) was superior to either alone for protecting renal function against acute kidney ischemia-reperfusion (IR; 40-min ischemia/27-h reperfusion) injury when complicated by sepsis syndrome (SS; by cecal-ligation-puncture). Adult-male Sprague-Dawley rats (n=40) were equally divided into group 1 (sham-control), group 2 (IR-SS), group 3 (IR-SS + Ex4, 10 μg/kg subcutaneously 30 min after reperfusion and daily for 3 days), group 4 [IR-SS + ADMSC (1.2 × 10)], and group 5 (IR-SS + Ex4 + ADMSC). The circulating levels of BUN and creatinine and the ratio of urine protein to creatinine were highest in group 2, lowest in group 1, significantly higher in groups 3 and 4 than group 5, and significantly higher in group 3 than in group 4 (all P<0.0001). Microscopic findings of kidney injury score, inflammatory cells (CD14+, F4/80+), and expressions of glomerular-damage indicators (FSP-1+/WT-1+) and renal tubular-damage indicators (KIM-1+/snail+) showed an identical pattern, whereas expressions of indices of glomerular-integrity (ZO-1+/p-cadherin+/podocin+/synaptopodin+) and angiogenesis (CD31+/vWF+/number of small vessels) biomarkers demonstrated an opposite pattern, to that of creatinine level (all P<0.001). Protein expressions of inflammatory (MMP-9/IL-1ß/TNF-α/TLR-2/TLR-4), apoptotic (cleaved caspase-3/PARP/mitochondrial Bax), and oxidative-stress (NOX-1/NOX-2/oxidized protein) biomarkers exhibited an identical pattern, whereas anti-inflammatory (IL-10/IL-4) biomarkers displayed an opposite pattern, to that of creatinine level (all P<0.001). In conclusion, combined Ex4 and ADMSC therapy significantly protected kidney from acute IR-SS injury.

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