Kim Say-June, Kim Ok-Hee, Hong Ha-Eun, Ju Ji Hyeon, Lee Do Sang
Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea.
Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea.
World J Gastrointest Surg. 2024 Mar 27;16(3):882-892. doi: 10.4240/wjgs.v16.i3.882.
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.
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.
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 and in a DSS-induced IBD mouse model.
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.
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.
炎症性肠病(IBD)是一种胃肠道的慢性炎症性疾病,肿瘤坏死因子(TNF)-α在其发病机制中起关键作用。依那西普是一种TNF的诱饵受体,用于治疗炎症性疾病。脂肪来源干细胞(ASC)分泌的蛋白质组具有抗炎作用,使其成为IBD有前景的治疗选择。
研究从合成依那西普的ASC获得的蛋白质组对结肠细胞和葡聚糖硫酸钠(DSS)诱导的IBD小鼠模型的抗炎作用。
用编码依那西普的微型环状质粒转染ASC以产生产生依那西普的细胞。然后在体外和DSS诱导的IBD小鼠模型中测试这些细胞的分泌物质的抗炎作用。
本研究揭示了有前景的结果,表明与对照蛋白质组(Ct-Sec)相比,用来自合成依那西普的ASC的蛋白质组处理的组[依那西普-蛋白质组(Et-Sec)组]中炎症介质如白细胞介素-6、单核细胞趋化蛋白-1和TNF-α的表达水平显著降低。此外,与Ct-Sec相比,Et-Sec组在保留肠组织结构方面表现出显著的治疗效果。
这些结果表明,合成依那西普的ASC分泌的蛋白质组有潜力作为治疗IBD的治疗剂,通过将ASC蛋白质组的抗炎特性与依那西普的靶向方法相结合,可能增强治疗效果,以更好地应对IBD多方面的病理生理学。