单位：[1]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[2]lnstitute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China[3]National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing 100101, China[4]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital ,National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China[5]Graduate School of Peking Union Medical College, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China[6]University of Chinese Academy of Sciences, Beijing 100049, China[7]National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing 100176, China[8]Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin 130061, China[9]institute of Clinical Medical Sciences, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China[10]lnstitute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China[11]Department of Cardiology, China-Japan Friendship Hospital, Beijing 100029, China[12]Medical University of Ha Er Bin, Ha'erbin, Heilongjiang 150081, China[13]International Stem Cell Banking Initiative, 2 High Street, Barley, Hertfordshire SG8 8HZ, UK[14]Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, The First Hospital of 川in University, Changchun,川in 130061, China[15]National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin 130061, China and 16Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
Lung injury and fibrosis represent the most significant outcomes of severe and acute lung disorders, including COVID-19. However, there are still no effective drugs to treat lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) produced under good manufacturing practice requirements, that can treat lung injury and fibrosis in vivo. We generate IMRCs by sequentially differentiating hESCs with serum-free reagents. IMRCs possess a unique gene expression profile distinct from that of umbilical cord mesenchymal stem cells (UCMSCs), such as higher expression levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through paracrine regulatory mechanisms. IMRCs are superior to both primary UCMSCs and the FDA-approved drug pirfenidone, with an excellent efficacy and safety profile in mice and monkeys. In light of public health crises involving pneumonia, acute lung injury and acute respiratory distress syndrome, our findings suggest that IMRCs are ready for clinical trials on lung disorders.
基金：
Beijing Municipal Science & Technology CommissionBeijing Municipal Science & Technology Commission [Z181100003818005]; National Key Research and Development Program [2018YFA0108400, 2017YFA0104403, 2017YFA0105001, 2016YFA0101502, 2020YFC0843900, 2020YFC0841900]; Strategic Priority Research Program of the Chinese Academy of SciencesChinese Academy of Sciences [XDA16030701, XDA16030401, XDA16040502]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31621004]; Key Research Projects of the Frontier Science of the Chinese Academy of Sciences [QYZDY-SSW-SMC002]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2019M660791]
第一作者单位：[1]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[2]lnstitute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China[3]National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing 100101, China
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[2]lnstitute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China[3]National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing 100101, China[4]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital ,National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China[5]Graduate School of Peking Union Medical College, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China[6]University of Chinese Academy of Sciences, Beijing 100049, China
推荐引用方式(GB/T 7714)：
Wu Jun,Song Dingyun,Li Zhongwen,et al.Immunity-and-matrix-regulatory cells derived from human embryonic stem cells safely and effectively treat mouse lung injury and fibrosis[J].CELL RESEARCH.2020,30(9):794-809.doi:10.1038/s41422-020-0354-1.
APA：
Wu, Jun,Song, Dingyun,Li, Zhongwen,Guo, Baojie,Xiao, Yani...&Hao, Jie.(2020).Immunity-and-matrix-regulatory cells derived from human embryonic stem cells safely and effectively treat mouse lung injury and fibrosis.CELL RESEARCH,30,(9)
MLA：
Wu, Jun,et al."Immunity-and-matrix-regulatory cells derived from human embryonic stem cells safely and effectively treat mouse lung injury and fibrosis".CELL RESEARCH 30..9(2020):794-809
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