细胞因子治疗优化的免疫治疗影响脐cord-derived MSC治疗炎症性肝脏疾病。
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德威特SFH,美利奴,Franquesa M, Strini T, van Zoggel JAA, Korevaar党卫军,六F, Gargesha M O 'Flynn L,罗伊·D Elliman SJ, Newsome PN,博安公司CC, Hoogduijn乔丹
细胞因子治疗优化的免疫治疗影响脐cord-derived MSC治疗炎症性肝脏疾病。
干细胞Res。2017年6月8日,8 (1):140。doi: 10.1186 / s13287 - 017 - 0590 - 6。
- PubMed ID
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28595619 (在PubMed]
- 文摘
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背景:间充质基质细胞(MSC)具有免疫调节特性和低免疫原性,关键属性为他们发展成一个有效的细胞免疫治疗。他们显示在临床试验中针对肝脏疾病;然而MSC治疗的疗效将受益于改善MSC的免疫调节和免疫原性属性。方法:来自人脐带MSC (ucMSC)治疗3天体外各种炎症因子,白细胞介素,维生素和血清剥夺。考察了他们的免疫原性和免疫调节能力的基因表达分析、表面标记表达式语言活动,PGE2分泌和抑制T细胞增殖和IFNgamma生产。此外,他们激活NK细胞的细胞毒性研究对NK细胞通过CD107a表达式。免疫调节能力,biodistribution和生存的预处理ucMSC CCl4-induced肝脏疾病小鼠模型研究。此外,预处理的MSC的能力改善肝脏炎症检查在一个体外肝脏炎症共培养模型。结果:IFN-gamma和多种细胞因子组成的鸡尾酒(MC) IFN-gamma, TGFbeta和视黄酸调节免疫调节因子的表达PD-L1我活动。随后,这两种治疗增强的能力ucMSC抑制CD4和CD8 T细胞增殖和IFN-gamma生产。 The susceptibility of ucMSC for NK cell lysis was decreased by IFN-beta, TGFbeta and MC treatment. In vivo, no immunomodulation was observed by the ucMSC. Four hours after intravenous infusion in mice with CCl4-induced inflammatory liver injury, the majority of ucMSC were trapped in the lungs. Rapid clearance of ucMSC(VitB6), ucMSC(Starv + VitB6) and ucMSC(MC) and altered bio-distribution of ucMSC(TGFbeta) compared to untreated ucMSC was observed. In the ex vivo co-culture system with inflammatory liver slices ucMSC(MC) showed significantly enhanced modulatory capacity compared to untreated ucMSC. CONCLUSIONS: The present study demonstrates the responsiveness of ucMSC to in vitro optimisation treatment. The observed improvements in immunomodulatory capacity as well as immunogenicity after MC treatment may improve the efficacy of ucMSC as immunotherapy targeted towards liver inflammation.
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