Ryu Da-Bin, Lim Ji-Young, Lee Sung-Eun, Park Gyeongsin, Min Chang-Ki
Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Immune Netw. 2016 Dec;16(6):358-365. doi: 10.4110/in.2016.16.6.358. Epub 2016 Dec 22.
Mesenchymal stem cells (MSCs) have been used experimentally for treating inflammatory disorders, partly owing to their immunosuppressive properties. The goal of the study was to determine whether TLR ligands can enhance the therapeutic efficacy of bone marrow-derived MSCs for the treatment of inflammatory bowel disease. Mice (C57BL6) were administered with 4% dextran sulfate sodium (DSS) in drinking water for 7 days and injected with MSCs on days 1 and 3 following DSS ingestion. Our results demonstrated that among various TLR ligands, MSCs treated with polyinosinic-polycytidylic acid [poly(I:C)], which is a TLR3 ligand, more profoundly induced IDO, which is a therapeutically relevant immunosuppressive factor, without any observable phenotype change . The poly(I:C)-treated MSCs attenuated the pathologic severity of DSS-induced murine colitis when injected i.p. but not i.v. In summary, preconditioning MSCs with poly(I:C) might improve their efficacy in treating DSS-induced colitis, and this effect at least partly depends on the enhancement of their immunosuppressive activity through increasing their production of IDO.
间充质干细胞(MSCs)已被用于炎症性疾病的实验性治疗,部分原因是其具有免疫抑制特性。本研究的目的是确定Toll样受体(TLR)配体是否能增强骨髓来源的间充质干细胞治疗炎症性肠病的疗效。给C57BL6小鼠饮用含4%葡聚糖硫酸钠(DSS)的水7天,并在摄入DSS后的第1天和第3天注射间充质干细胞。我们的结果表明,在各种TLR配体中,用TLR3配体聚肌苷酸-聚胞苷酸[poly(I:C)]处理的间充质干细胞更显著地诱导吲哚胺2,3-双加氧酶(IDO),IDO是一种具有治疗相关性的免疫抑制因子,且未观察到任何明显的表型变化。经poly(I:C)处理的间充质干细胞腹腔注射而非静脉注射时,可减轻DSS诱导的小鼠结肠炎的病理严重程度。总之,用poly(I:C)预处理间充质干细胞可能会提高其治疗DSS诱导的结肠炎的疗效,且这种效应至少部分取决于通过增加IDO的产生来增强其免疫抑制活性。