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Combination therapy of exendin-4 and allogenic adipose-derived mesenchymal stem cell preserved renal function in a chronic kidney disease and sepsis syndrome setting in rats

Authors :
Pei-Hsun Sung
Cheuk-Kwan Sun
Hon-Kan Yip
Chih-Hung Chen
Kuan-Hung Chen
Jiunn-Jye Sheu
Chih-Chao Yang
Pei-Lin Shao
Mel S. Lee
Kun-Chen Lin
Ben-Chung Cheng
Hsin-Ju Chiang
Hsueh-Wen Chang
Source :
Oncotarget
Publication Year :
2017
Publisher :
Impact Journals, LLC, 2017.

Abstract

Combined therapy with exendin-4 (Ex4) and allogenic adipose-derived mesenchymal stem cells (ADMSC) was tested against either therapy alone for protecting kidney function against chronic kidney disease (CKD) complicated by sepsis syndrome (SS) [i.e., by intraperitoneal injection of cecal-derived bacteria (1.0 × 104) cells/milliliter/total 5.0 cc].Adult-male-Sprague Dawley rats (n=36) were equally divided into group 1 (sham-control), group 2 (CKD), group 3 (CKD-SS), group 4 (CKD-SS-Ex4), group 5 (CKD-SS-ADMSC) and group 6 (CKD-SS-Ex4-ADMSC). At day 42 after CKD induction SS was induced. Thirty-minutes after SS induction, ADMSCs (2.0 ×106 cells) were intravenously administered to groups 5 and 6. Ex4 (10 μg/kg) was intraperitoneally administered groups 4 and 6 at 30 min and days 1 to 5 after SS induction. Animals were euthanized at day 47 after CKD induction. Kidney-injury score, collagen-deposition area, and creatinine/BUN levels were lowest in group 1, highest in group 3 and significantly higher in group 2 than in groups 4 to 6 in a progressively increasing manner (all P0.0001). Cellular expressions of inflammatory (CD14/CD68) and glomerulus/tubular-injury (WT-1/KIM-1) biomarkers displayed an identical pattern, whereas glomerulus/podocyte-component (dystroglycan/nephrin/ZO-1/fibronectin/p-cadherin) biomarkers showed an opposite kidney-injury score among the six groups (all P

Details

ISSN :
19492553
Volume :
8
Database :
OpenAIRE
Journal :
Oncotarget
Accession number :
edsair.doi.dedup.....cfb4f8c0f8c54f16c5ac648972a554fd
Full Text :
https://doi.org/10.18632/oncotarget.21727