Apoptotic adipose-derived mesenchymal stem cell therapy protects against lung and kidney injury in sepsis syndrome caused by cecal ligation puncture in rats

作者：Sung, Pei Hsun; Chang, Chia Lo; Tsai, Tzu Hsien; Chang, Li Teh; Leu, Steve; Chen, Yung Lung; Yang, Chic Chao; Chua, Sarah; Yeh, Kuo Ho; Chai, Han Tan; Chang, Hsueh Wen; Chen, Hong Hwa^*; Yip, Hon Kan

来源：Stem Cell Research & Therapy, 2013, 4(6): 155.

DOI：10.1186/scrt385

Introduction: 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-alpha 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-alpha, NF-kappa B), 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 (gamma-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.

• 出版日期2013-12-25
• 单位中山大学; 长春大学