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

To evaluate the therapeutic effects of IMRCs on lung injury and fibrosis, IMRCs were administered 496 intravenously into a bleomycin-induced model of lung injury. IMRCs ameliorated the total body weight 497 reduction in mice exposed to bleomycin (BLM)-induced lung injury, in a dose-dependent manner (Fig. 498 6B ). Kaplan-Meier survival curves indicated that IMRC treatment prolonged the overall survival rates 499 (BLM group 12.5% vs. 1×10 6 IMRCs 25%, 3×10 6 IMRCs 50%, 5×10 6 IMRCs 62.5% (P＜0.01)) and 500 the median survival time (BLM group 11.5d vs. 1×10 6 IMRCs 15.5d, 3×10 6 IMRCs 18d, 5×10 6 IMRCs 501 21d) in mice exposed to bleomycin-induced lung injury. There was a statistically significant difference 502 between the BLM group and the 5×10 6 IMRCs group, but not the other groups (Fig. 6C) . Histological 503 staining of the lung at 21 days after bleomycin injection (inflammation phase) showed diffuse pneumonic 504 lesions with loss of the normal alveolar architecture, septal thickening, enlarged alveoli, and increased 505 infiltration of inflammatory cells in the interstitial and peribronchiolar areas, in the BLM lung compared 506 with normal lung. IMRC treatment reduced alveolar thickening in the lung in a dose-dependent manner 507 ( Fig. 6D-F) . Moreover, IMRC treatment reduced the number of macrophage in the lung (Fig. 6F) . These 508 results indicated that IMRC treatment can reduce inflammation in the lung after acute injury. Moreover, 509 IMRC treatment also improved the Ashcroft score for pulmonary fibrosis in a dose-dependent manner 510 (Fig. 6G) . In particularly, IMRC treatment decreased collagen deposition in the BLM lung in a dose-511 author/funder. All rights reserved. No reuse allowed without permission.