Immunity-and-Matrix-Regulatory Cells Derived from Human Embryonic Stem Cells Safely and Effectively Treat Mouse Lung Injury and Fibrosis

Jun Wu; Dingyun Song; Zhongwen Li; Baojie Guo; Yani Xiao; Wenjing Liu; Lingmin Liang; Chunjing Feng; Tingting Gao; Zai Wang; Jianyan Wen; Shengnan Yang; Peipei Liu; Lei Wang; Yukai Wang; Liang Peng; Guihai Feng; Shiqiang Huang; Glyn Nigel Stacey; Wei Li; Yan Huo; Ronghua Jin; Qi Zhou; Liu Wang; Baoyang Hu; Huaping Dai; Jie Hao

repair. Accordingly, expression of the T cell-suppressive IDO1 greatly increased in IMRCs after 585 stimulation with the pro-inflammatory cytokine IFN-γ, even more than UCMSCs. Genome-wide RNA 586 sequencing revealed that IMRCs and UCMSCs had different expression profiles after exposure to IFN-587 γ. Analysis of the secretomes of IMRCs and UCMSCs confirmed at least nine pro-inflammatory 588 cytokines that were lower, and several anti-inflammatory cytokines and pro-regenerative factors that 589 were higher in IMRCs than UCMSCs. All these results suggested that IMRCs possess a hyper-590 immunomodulatory capacity compared to primary UCMSCs, after stimulation with IFN-γ. Thus, these 591 cells can be administered to immunocompetent animals and human patients without the need for further 592 immunosuppression. 593