Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Mar 27, 2024; 16(3): 882-892
Published online Mar 27, 2024. doi: 10.4240/wjgs.v16.i3.882
Etanercept-synthesizing adipose-derived stem cell secretome: A promising therapeutic option for inflammatory bowel disease
Say-June Kim, Ok-Hee Kim, Ha-Eun Hong, Ji Hyeon Ju, Do Sang Lee
Say-June Kim, Do Sang Lee, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
Say-June Kim, Ok-Hee Kim, Ha-Eun Hong, Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
Ji Hyeon Ju, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
Author contributions: Lee DS was responsible for planning the study, data interpretation, and manuscript preparation; Kim SJ wrote the article, conducted experiments, and participated in data analysis and interpretation; Kim OH, Ju JH, and Hong HE participated in the in vitro and in vivo experiments and analysis and interpretation of data; All authors read and approved the manuscript.
Supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT), No. NRF-2021R1F1A1064566.
Institutional review board statement: Human adipose-derived stem cells were acquired from Hurim BioCell Co., Seoul, Republic of Korea, Institutional Review Board No. 700069-201407-BR-002-01.
Institutional animal care and use committee statement: Five-week-old male BALB/c mice, sourced from Orient Bio (Seongnam, Republic of Korea), were used in this animal experiment, conducted in compliance with the Institute for Laboratory Animal Research guidelines at the Catholic University of Korea, Institutional Review Board No. CUMC- 2022-0020-01.
Conflict-of-interest statement: Dr. Lee reports grants from National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT), during the conduct of the study; In addition, Dr. Lee has a patent 10-2023-0193643 pending to Catholic University Industry-Academic Cooperation Foundation.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Do Sang Lee, MD, PhD, Doctor, Professor, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, South Korea. dosangs@catholic.ac.kr
Received: November 9, 2023
Peer-review started: November 9, 2023
First decision: December 8, 2023
Revised: January 3, 2024
Accepted: February 3, 2024
Article in press: February 3, 2024
Published online: March 27, 2024
Abstract
BACKGROUND

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, with tumor necrosis factor (TNF)-α playing a key role in its pathogenesis. Etanercept, a decoy receptor for TNF, is used to treat inflammatory conditions. The secretome derived from adipose-derived stem cells (ASCs) has anti-inflammatory effects, making it a promising therapeutic option for IBD.

AIM

To investigate the anti-inflammatory effects of the secretome obtained from ASCs synthesizing etanercept on colon cells and in a dextran sulfate sodium (DSS)-induced IBD mouse model.

METHODS

ASCs were transfected with etanercept-encoding mini-circle plasmids to create etanercept-producing cells. The secretory material from these cells was then tested for anti-inflammatory effects both in vitro and in a DSS-induced IBD mouse model.

RESULTS

This study revealed promising results indicating that the group treated with the secretome derived from etanercept-synthesizing ASCs [Etanercept-Secretome (Et-Sec) group] had significantly lower expression levels of inflammatory mediators, such as interleukin-6, Monocyte Chemoattractant Protein-1, and TNF-α, when compared to the control secretome (Ct-Sec). Moreover, the Et-Sec group exhibited a marked therapeutic effect in terms of preserving the architecture of intestinal tissue compared to the Ct-Sec.

CONCLUSION

These results suggest that the secretome derived from ASCs that synthesize etanercept has potential as a therapeutic agent for the treatment of IBD, potentially enhancing treatment efficacy by merging the anti-inflammatory qualities of the ASC secretome with etanercept's targeted approach to better address the multifaceted pathophysiology of IBD.

Keywords: Adipose-derived stem cells, Etanercept, Inflammatory bowel disease, Secretome, Tumor necrosis factor-α

Core Tip: This study explores a promising therapeutic strategy for treating inflammatory bowel disease (IBD) by harnessing the potential of a secretome derived from adipose-derived stem cells (ASCs) engineered to produce etanercept, a tumor necrosis factor-blocking drug. The findings demonstrate that the Etanercept-Secretome (Et-Sec) offers enhanced anti-inflammatory effects compared to traditional etanercept treatment. This superior therapeutic potential of the Et-Sec in IBD is attributed to its unique combination of etanercept synthesis and the intrinsic anti-inflammatory and immunomodulatory properties of ASC secretome, making it a promising candidate for advanced IBD therapy.