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

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.15.042119 doi: bioRxiv preprint 22 showed that no colonies were formed by IMRCs. In addition, the somatic mutation analysis by whole 568 genome sequencing also showed no mutations in proto-oncogenes and tumor suppressor genes, nor any 569 coding and non-coding exon regions of IMRCs. These results indicated that IMRCs have no 570 demonstrable potential to form tumors. Moreover, IMRCs could not undergo long-term engraftment and 571 disappeared around day 46. IMRCs did not transdifferentiate into endothelial cells nor alveolar epithelial 572 cells in the lung. To evaluate the risks of clinical application, short-and long-term toxicity tests were 573 performed in cynomolgus monkeys. After 6 months, both acute toxicity tests and long-term toxicity test 574 data showed that no abnormalities were observed. These results proved that IMRCs could have an 575 excellent safety profile and clinical potential. Moreover, the above data suggested that the therapeutic 576 efficacy of IMRCs may not be due to long-term engraftment and direct repair of tissue, but due to their 577 hyper-immunomodulatory and anti-fibrotic functions at inflammatory sites of tissue interstitium. 578