Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2021; 27(23): 3342-3356
Published online Jun 21, 2021. doi: 10.3748/wjg.v27.i23.3342
Conditioned secretome of adipose-derived stem cells improves dextran sulfate sodium-induced colitis in mice
Seunghun Lee, Jeonghoon Heo, Eun-Kyung Ahn, Jae Hyun Kim, Young-Ho Kim, Hee-Kyung Chang, Sang-Joon Lee, Jongsik Kim, Seun-Ja Park
Seunghun Lee, Department of Colorectal Surgery, Kosin University College of Medicine, Busan 49267, South Korea
Jeonghoon Heo, Eun-Kyung Ahn, Young-Ho Kim, Department of Molecular Biology and Immunology, Kosin University College of Medicine, Busan 49267, South Korea
Jae Hyun Kim, Seun-Ja Park, Department of Gastroenterology, Kosin University College of Medicine, Busan 49267, South Korea
Hee-Kyung Chang, Department of Pathology, Kosin University College of Medicine, Busan 49267, South Korea
Sang-Joon Lee, Department of Ophthalmology, Kosin University College of Medicine, Busan 49267, South Korea
Jongsik Kim, Department of Anatomy, Kosin University College of Medicine, Busan 49267, South Korea
Author contributions: Lee S, Ahn EK, Park SJ and Heo J designed the study; Lee S, Ahn EK, Chang HK, Kim J, Park SJ and Heo J performed the research; Lee S, Ahn EK, Kim JH, Kim YH, Lee SJ, Park SJ and Heo J participated in the interpretation of the data; Lee S, Ahn EK, Park SJ and Heo J wrote paper; Chang HK, Kim YH, Lee SJ, Kim J, Park SJ and Heo J supervised the analysis; all authors approved the final version.
Supported by National Research Foundation of Korea (NRF) grants funded by the Korea Government (MSIT), No. 2017R1A2B2011956 and No. 2019R1F1A1061453.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee at Kosin University College of Medicine (IACUC protocol number: Kosin15-12).
Conflict-of-interest statement: None of the authors have any conflicts of interest to declare.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Seun-Ja Park, MD, PhD, Professor, Department of Gastroenterology, Kosin University College of Medicine, 262 Gamcheon-ro, Seogu, Busan 49267, South Korea. parksj@kosinmed.or.kr
Received: February 4, 2021
Peer-review started: February 4, 2021
First decision: February 24, 2021
Revised: March 5, 2021
Accepted: May 19, 2021
Article in press: May 19, 2021
Published online: June 21, 2021
Processing time: 134 Days and 2.7 Hours
Abstract
BACKGROUND

Inflammatory bowel diseases (IBD) is related to uncontrolled immune response. Currently, there is no successful treatment for significant improvement in IBD. Stem cells display their therapeutic effects through their repopulating capacity or secreting factors.

AIM

To investigate the effects of conditioned mouse adipose-derived stem cells (mADSCs) secretome on colitis-induced mice.

METHODS

mADSCs were isolated from adipose tissue of C57BL/6 mice. Conditioned mADSCs secrectome was obtained by culturing of mADSCs with lipopolysaccharides (LPS, 1 μg/mL) for 24 h. Acute colitis was induced by 2% dextran sulfate sodium (DSS) drinking water for 7 d and then normal drinking water for 4 d. The mice were treated with normal culture medium (NM group), conditioned mADSCs secretome (CM group) or mADSCs (SC group). The length of colon and histopatholgy of colon tissues were evaluated. The mRNA expression levels of inflammatory cytokines in colon tissue and the serum interleukin (IL)-6 levels were determined.

RESULTS

The isolated mADSCs maintained the mADSCs specific gene expression profiles during experiment. The conditioned mADSCs secretome released by the treatment of mADSCs with LPS contained mainly inflammatory chemokines, colony-stimulating factors and inflammatory cytokines. The loss of body weight and reduction in colon length were ameliorated in the CM group. The conditioned mADSCs secretome reduced the histological score in colon tissue. The expression of IL-1b and IL-6 mRNAs in colon tissues significantly inhibited in the CM group compared to SC group and NM group, respectively. The elevation of serum IL-6 levels was also ameliorated in the CM group. These results indicate that the conditioned mADSCs secretome suppressed the synthesis of inflammatory cytokines in damaged colon tissue and the elevation of serum IL-6 concentration in DSS-induced mice

CONCLUSION

Conditioned mADSCs secretome might play regenerative roles by the suppression of IL-6 in serum and tissue during acute colitis, and may be more effective than stem cells themselves in the regeneration of colon tissue.

Keywords: Adipose-derived stem cells; Conditioned secretome; Cytokines; Interleukin-6; Colitis; Regeneration

Core Tip: The therapeutic ability of mesenchymal stem cells (MSCs) is mostly mediated by their paracrine effects. Cell free therapy using MSCs secretome could be more promising strategy than stem cells based therapy. The present study demonstrates that the conditioned secretome of adipose–derived stem cells (ADSCs) has more efficient effects for improving acute colitis in dextran sulfate-sodium-induced mouse model. The effects by the conditioned secretome of ADSCs were mediated by suppression of interleukin (IL)-6 mRNA synthesis in colon tissue and serum IL-6 protein levels, which suggests that the stem cell secretome may have efficient therapeutic potential for incurable inflammatory bowel diseases.