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The exhaustion of airway epithelial stem cells plays a pathogenetic role in silicosis. In present study, we investigated therapeutic effects and potential mechanism of human embryonic stem cell (hESC)\u2010derived MSC\u2010likes immune and matrix regulatory cells (IMRCs) (hESC\u2010MSC\u2010IMRCs), a type of manufacturable MSCs for clinical application in silicosis mice. Our results showed that the transplantation of hESC\u2010MSC\u2010IMRCs led the alleviation of silica\u2010induced silicosis in mice, accompanied by inhibiting epithelia\u2010mesenchymal transition (EMT), activating B\u2010cell\u2010specific Moloney murine leukemia virus integration site 1 (Bmi1) signaling and airway epithelial cell regeneration. In consistence, the secretome of hESC\u2010MSC\u2010IMRC exhibited abilities to restore the potency and plasticity of primary human bronchial epithelial cells (HBECs) proliferation and differentiation following the SiO<jats:sub>2<\/jats:sub>\u2010induced HBECs injury. Mechanistically, the secretome resolved the SiO<jats:sub>2<\/jats:sub>\u2010induced HBECs injury through the activation of BMI1 signaling and restoration of airway basal cell proliferation and differentiation. Moreover, the activation of BMI1 significantly enhanced the capacity of HBEC proliferation and differentiation to multiple airway epithelial cell types in organoids. Cytokine array revealed that DKK1, VEGF, uPAR, IL\u20108, Serpin E1, MCP\u20101 and Tsp\u20101 were the main factors in the hESC\u2010MSC\u2010IMRC secretome. These results demonstrated a potential therapeutic effect of hESC\u2010MSC\u2010IMRCs and their secretome for silicosis, in part through a mechanism by activating Bmi1 signaling to revert the exhaustion of airway epithelial stem cells, subsequentially enhance the potency and plasticity of lung epithelial stem cells.<\/jats:p>","DOI":"10.1002\/tox.23833","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T15:30:21Z","timestamp":1685028621000},"page":"2084-2099","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Human embryonic stem cell\u2010derived mesenchymal stem cell secretome reverts silica\u2010induced airway epithelial cell injury by regulating <scp>Bmi1<\/scp> signaling"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7316-9259","authenticated-orcid":false,"given":"Jiali","family":"Yang","sequence":"first","affiliation":[{"name":"Ningxia Clinical Research Institute Center Laboratory, People's Hospital of Ningxia Hui Autonomous Region  Yinchuan China"},{"name":"Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western College of Life Science, Ningxia University  Yinchuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Xue","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western College of Life Science, Ningxia University  Yinchuan China"},{"name":"General Hospital of Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenfeng","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western College of Life Science, Ningxia University  Yinchuan China"},{"name":"Zephyrm Biotechnologies Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western College of Life Science, Ningxia University  Yinchuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranran","family":"Xu","sequence":"additional","affiliation":[{"name":"Zephyrm Biotechnologies Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western College of Life Science, Ningxia University  Yinchuan China"},{"name":"Department of Anatomy and Cell Biology Carver College of Medicine, University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Ningxia Clinical Research Institute Center Laboratory, People's Hospital of Ningxia Hui Autonomous Region  Yinchuan China"},{"name":"Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western College of Life Science, Ningxia University  Yinchuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western College of Life Science, Ningxia University  Yinchuan China"},{"name":"Department of Anatomy and Cell Biology Carver College of Medicine, University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Zephyrm Biotechnologies Co., Ltd.  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