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

doi:10.4240/wjgs.v16.i3.882

Etanercept-synthesizing adipose-derived stem cell secretome: A promising therapeutic option for inflammatory bowel disease

World J Gastrointest Surg. 2024 Mar 27;16(3):882-892. doi: 10.4240/wjgs.v16.i3.882.

Authors

Say-June Kim^{1

2}, Ok-Hee Kim², Ha-Eun Hong², Ji Hyeon Ju³, Do Sang Lee⁴

Affiliations

¹ Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea.
² Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea.
³ Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea.
⁴ Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea. dosangs@catholic.ac.kr.

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.