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

Chia Lo Chang, Chih Hung Chen, John Y. Chiang, Cheuk Kwan Sun, Yi Ling Chen, Kuan Hung Chen, Pei Hsun Sung, Tien Hung Huang, Yi Chen Li, Hong Hwa Chen, Hon Kan Yip*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

29 Scopus citations

Abstract

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.

Original languageEnglish
Article numberAJTR0092470
Pages (from-to)2706-2724
Number of pages19
JournalAmerican Journal of Translational Research
Volume11
Issue number5
StatePublished - 2019

Bibliographical note

Publisher Copyright:
© 2019, E-Century Publishing Corporation. All rights reserved.

Keywords

  • Acute colitis
  • Dextran sulfate sodium
  • Exosom
  • Inflammation
  • Melatonin
  • Oxidative stress

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