Deng Zhenhua, Zhou Jinren, Mu Xiaoxin, Gu Jian, Li Xiangyu, Shao Qing, Li Jinyang, Yang Chao, Han Guoyong, Zhao Jie, Xia Yongxiang
Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Liver Cancer Institute, Nanjing Medical University, Nanjing, China.
Front Cell Dev Biol. 2021 Oct 12;9:737825. doi: 10.3389/fcell.2021.737825. eCollection 2021.
Liver fibrosis is a progression stage of chronic liver disease, while current therapies cannot cure or attune cirrhosis effectively. Human amniotic mesenchymal stromal cell (hAMSC) presented immunoregulatory and tissue repairability of multiple illnesses. Regulatory T cells (Treg) had been proved to be functional in reducing immune cell activity. We showed that co-infusion of hAMSC and Treg prevented mild liver fibrosis comparing with hAMSC or Treg alone group. study indicated that the addition of Treg or the supernatant of Treg improved the hepatocyte growth factor (HGF) secreting and cell differentiation ability of hAMSC. Reduction of TGF-β significantly decreased the HGF secreting and differentiation of hAMSC. Multiple signal neutralizers were added to the culture to understand further the mechanism, which showed that 1-MT, the suppressor of Indoleamine 2,3-dioxygenase (IDO), was involved in the effect of TGF-β in regulating hAMSC. Depletion of TGF-β or IDO signaling successfully abolished the effect of Treg in improving hAMSC's function both and vivo. Finally, our result indicated that Treg improved the function of hAMSC by regulating the TGF-β-IDO signaling and co-infusion of hAMSC and Treg provided a promising approach for treating liver cirrhosis.
肝纤维化是慢性肝病的一个进展阶段，而目前的治疗方法无法有效治愈或调节肝硬化。人羊膜间充质基质细胞（hAMSC）具有多种疾病的免疫调节和组织修复能力。调节性T细胞（Treg）已被证明在降低免疫细胞活性方面发挥作用。我们发现，与单独使用hAMSC或Treg的组相比，联合输注hAMSC和Treg可预防轻度肝纤维化。研究表明，添加Treg或Treg的上清液可提高hAMSC分泌肝细胞生长因子（HGF）的能力和细胞分化能力。TGF-β的减少显著降低了hAMSC分泌HGF的能力和分化。在培养物中添加多种信号中和剂以进一步了解其机制，结果表明，吲哚胺2,3-双加氧酶（IDO）的抑制剂1-MT参与了TGF-β对hAMSC的调节作用。TGF-β或IDO信号通路的缺失成功消除了Treg在体内外改善hAMSC功能的作用。最后，我们的结果表明，Treg通过调节TGF-β-IDO信号通路改善了hAMSC的功能，联合输注hAMSC和Treg为治疗肝硬化提供了一种有前景的方法。
