School of Medicine, Jiangsu University, Zhenjiang 212013, China.
School of Medicine, Jiangsu University, Zhenjiang 212013, China.
Int Immunopharmacol. 2024 Nov 15;141:112883. doi: 10.1016/j.intimp.2024.112883. Epub 2024 Aug 16.
Ectodermal mesenchymal stem cells-derived conditioned medium (EMSCs-CM) has been reported to protect against ulcerative colitis (UC) in mice, but its underlying mechanism in alleviating UC need to be further elucidated. Here, it is reported that EMSCs-CM could attenuate pro-inflammatory response of LPS-induced IEC-6 cells and regulate the polarization of macrophages towards anti-inflammatory type in vitro. Furthermore, PLGA microspheres prepared by the double emulsion method were constructed for oral delivery of EMSCs-CM (EMSCs-CM-PLGA), which are beneficial for colon-targeted adhesion of EMSCs-CM to the damaged colon mucosa. The results showed that orally-administered of EMSCs-CM-PLGA microspheres reduced inflammatory cells infiltration and maintained the intestinal mucosal barrier. Further investigation found that EMSCs-CM-PLGA microspheres treatment gradually inhibited the activation of NF-κB pathway to regulate M1/M2 polarization balance in colon tissue macrophages, thereby alleviating DSS-induced UC. These results of this study will provide a theoretical basis for clinical application of EMSCs-CM in UC repair.
外胚层间充质干细胞衍生的条件培养基 (EMSCs-CM) 已被报道可保护小鼠免受溃疡性结肠炎 (UC) 的侵害，但它在缓解 UC 方面的潜在机制仍需进一步阐明。在这里，据报道 EMSCs-CM 可减轻 LPS 诱导的 IEC-6 细胞的促炎反应，并在体外调节巨噬细胞向抗炎型的极化。此外，通过复乳法制备的 PLGA 微球被构建用于 EMSCs-CM（EMSCs-CM-PLGA）的口服递送，这有利于 EMSCs-CM 对受损结肠黏膜的结肠靶向粘附。结果表明，口服给予 EMSCs-CM-PLGA 微球可减少炎症细胞浸润并维持肠黏膜屏障。进一步的研究发现，EMSCs-CM-PLGA 微球治疗可逐渐抑制 NF-κB 通路的激活，调节结肠组织巨噬细胞中 M1/M2 极化平衡，从而缓解 DSS 诱导的 UC。本研究的结果将为 EMSCs-CM 在 UC 修复中的临床应用提供理论基础。
