Apoptotic adipose-derived mesenchymal stem cell therapy protects against lung and kidney injury in sepsis syndrome caused by cecal ligation puncture in rats.
BACKGROUND
We tested the hypothesis that apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) are superior to healthy (H)-ADMSC in attenuating cecal ligation puncture (CLP)-induced sepsis-mediated lung and kidney injuries.


METHODS
Adult male rats divided into group 1 (sham controls), group 2 (CLP), group 3 [CLP + H-ADMSC administered at 0.5, 6, and 18 hours after CLP], and group 4 [CLP + A-ADMSC administered as in group 3] were sacrificed 72 hours after CLP with blood, lung, and kidney collected for studies.


RESULTS
White blood cell (WBC) count, circulating TNF-α and creatinine levels were higher in groups 2 and 3 than in groups 1 and 4 (all P < 0.001). Kidney and lung damage scores were highest in group 2, lowest in group 1, significantly higher in group 3 than in group 4 (all P < 0.0001). Protein expressions of inflammatory (ICAM-1, MMP-9, TNF-α, NF-κB), oxidative, and apoptotic (Bax, caspase-3, PARP) biomarkers were higher in groups 2 and 3 than groups 1 and 4, whereas anti-apoptotic (Bcl-2) and mitochondrial integrity (cytochrome-C) biomarkers were lower in groups 2 and 3 than in groups 1 and 4 (all P < 0.001). Expressions of anti-oxidant biomarkers at protein (GR, GPx, NQO-1, HO-1) and cellular (GR, GPx) levels were highest in group 4 (all P < 0.001). The number of inflammatory cells (CD3+) in lungs and levels of DNA damage marker (γ-H2AX) in kidneys were higher in groups 2 and 3 than in groups 1 and 4 (all P < 0.001).


CONCLUSIONS
A-ADMSC therapy was superior to H-ADMSC therapy in protecting major organs from damage in rats with CLP-induced sepsis syndrome.
Pei-Hsun
PH
Sung
Chia-Lo
CL
Chang
Tzu-Hsien
TH
Tsai
Li-Teh
LT
Chang
Steve
S
Leu
Yung-Lung
YL
Chen
Chic-Chao
CC
Yang
Sarah
S
Chua
Kuo-Ho
KH
Yeh
Han-Tan
HT
Chai
Hsueh-Wen
HW
Chang
Hong-Hwa
HH
Chen
Hon-Kan
HK
Yip
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D002432:Cecum / Q000293:injuries; D064987:Cell- and Tissue-Based Therapy; D003404:Creatinine / Q000097:blood; D007416:Intestinal Perforation / Q000150:complications; D007668:Kidney / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D007958:Leukocyte Count; D055370:Lung Injury / Q000378:metabolism* / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008928:Mitochondria / Q000378:metabolism; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood
D015415:Biomarkers; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine