Synergistic effect of combined melatonin and adipose-derived mesenchymal stem cell (ADMSC)-derived exosomes on amelioration of dextran sulfate sodium (DSS)-induced acute colitis

American Journal of Translational Research

Tien-Hung Huang¹  Kuan-Hung Chen²  John Y Chiang³  Cheuk-Kwan Sun⁴  Yi-Chen Li⁵  Hong-Hwa Chen⁶  Yi-Ling Chen⁷  Chia-Lo Chang⁸  Chih-Hung Chen⁹  Pei-Hsun Sung^1,10 

[1] Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan;Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, Kaohsiung 82445, Taiwan;Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan;Department of Nursing, Asia University, Taichung 41354, Taiwan;Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan

关键词: Dextran sulfate sodium;    acute colitis;    inflammation;    oxidative stress;    melatonin;    exosome;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

This study tested the hypothesis that melatonin (Mel) and adipose-derived mesenchymal stem cell-derived exosomes effectively suppress dextran sulfate sodium (DSS)-induced acute inflammatory colitis (AIC) in rats. To determine whether Mel-exosome treatment could ameliorate the severity of AIC, we treated Sprague Dawley rats with DSS-induced AIC with Mel, exosomes, or combined Mel-exosome therapy and evaluated the effects on AIC. First, to induce an inflammatory response in vitro, we treated HT-29 cells with lipopolysaccharide (LPS) and evaluated the response to Mel and/or exosome treatment. We found that expression of NOX-1, NOX-2, MMP-9, NF-κB, iNOS, ICAM-1, and COX-2 was significantly higher in HT-29 cells treated with LPS than in control cells, and was significantly reduced by either exosome or Mel treatment (P<0.001 for all). In vivo, flow cytometric analysis showed that, compared to untreated rats with AIC, the number of circulating inflammatory cells was lowest in rats treated with combined Mel-exosome treatment than in rats treated with either Mel or exosomes alone (P<0.0001). Compared with controls, as well as Mel or exosome treatment alone, combined Mel-exosome treatment ameliorated the effects of DSS-induced AIC as evidenced by changes in the expression of markers for inflammation, oxidative stress, apoptosis, and fibrosis (P<0.0001 for all). Additionally, histopathological findings showed that colon injury score, expression of inflammatory and DNA-damage markers, and bloody stool were all improved following combined Mel-exosome treatment (P<0.0001 for all). In conclusion, combined Mel-exosome treatment significantly protected the rat colon against DSS-induced AIC injury.

【 授权许可】

CC BY-NC