Impact of apoptotic adipose-derived mesenchymal stem cells on attenuating organ damage and reducing mortality in Rat sepsis syndrome induced by cecal puncture and ligation

Journal of Translational Medicine

Research

Steve Leu¹  Hon-Kan Yip²  Hsin-Ching Sung³  Chia-Hung Yen⁴  Chung-Lung Cho⁵  Cheuk-Kwan Sun⁶  Yen-Yi Zhen⁷  Sheng-Ying Chung⁷  Han-Tan Chai⁷  Tzu-Hsien Tsai⁷  Chia-Lo Chang⁸  Angela Chen⁹ 

[1] Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Republic of China, Taiwan;Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Republic of China, Taiwan;Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Republic of China, Taiwan;Department of Anatomy, Chang Gung University, Taoyuan, Republic of China, Taiwan;Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Republic of China, Taiwan;Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Republic of China, Taiwan;Department of Emergency Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Republic of China, Taiwan;Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Republic of China, Taiwan;Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Republic of China, Taiwan;Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Republic of China, Taiwan;

关键词: Left Ventricular Myocardium;    Late Apoptosis;    Sepsis Syndrome;    Sham Procedure;    Mesenchymal Stem Cell Therapy;   

DOI  :  10.1186/1479-5876-10-244

 received in 2012-09-25, accepted in 2012-11-28,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundWe tested whether apoptotic adipose-derived mesenchymal stem cells (A-ADMSCs) were superior to healthy (H)-ADMSCs at attenuating organ damage and mortality in sepsis syndrome following cecal ligation and puncture (CLP).MethodsAdult male rats were categorized into group 1 (sham control), group 2 (CLP), group 3 [CLP + H-ADMSC administered 0.5, 6, and 18 h after CLP], group 4 [CLP + A-ADMSC administered as per group 3].ResultsCirculating peak TNF-α level, at 6 h, was highest in groups 2 and 3, and higher in group 4 than group 1 (p < 0.0001). Immune reactivity (indicated by circulating and splenic helper-, cytoxic-, and regulatory-T cells) at 24 and 72 h exhibited the same pattern as TNF-α amongst the groups (all p < 0.0001). The mononuclear-cell early and late apoptosis level and organ damage parameters of liver (AST, ALT), kidney (creatinine) and lung (arterial oxygen saturation) also displayed a similar pattern to TNF-α levels (all p < 0.001). Protein levels of inflammatory (TNF-α, MMP-9, NF-κB, ICAM-1), oxidative (oxidized protein) and apoptotic (Bax, caspase-3, PARP) biomarkers were higher in groups 2 and 3 than group 1, whereas anti-apoptotic (Bcl-2) biomarker was lower in groups 2 and 3 than in group 1 but anti-oxidant (GR, GPx, HO-1, NQO-1) showed an opposite way of Bcl-2; these patterns were reversed for group 4 (all p < 0.001). Mortality was highest in group 3 and higher in group 2 than group 4 than group 1 (all p < 0.001).ConclusionsA-ADMSC therapy protected major organs from damage and improved prognosis in rats with sepsis syndrome.

【 授权许可】

Unknown   
© Chang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.