Journal article
Human embryonic stem cell-derived mesenchymal stem cell secretome reverts silica-induced airway epithelial cell injury by regulating Bmi1 signaling
Environmental toxicology, Vol.38(9), pp.2084-2099
09/2023
DOI: 10.1002/tox.23833
PMID: 37227716
Abstract
Silicosis is an irreversible chronic pulmonary disease caused by long-term inhalation and deposition of silica particles, which is currently incurable. 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)-derived MSC-likes immune and matrix regulatory cells (IMRCs) (hESC-MSC-IMRCs), a type of manufacturable MSCs for clinical application in silicosis mice. Our results showed that the transplantation of hESC-MSC-IMRCs led the alleviation of silica-induced silicosis in mice, accompanied by inhibiting epithelia-mesenchymal transition (EMT), activating B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) signaling and airway epithelial cell regeneration. In consistence, the secretome of hESC-MSC-IMRC exhibited abilities to restore the potency and plasticity of primary human bronchial epithelial cells (HBECs) proliferation and differentiation following the SiO
-induced HBECs injury. Mechanistically, the secretome resolved the SiO
-induced 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-8, Serpin E1, MCP-1 and Tsp-1 were the main factors in the hESC-MSC-IMRC secretome. These results demonstrated a potential therapeutic effect of hESC-MSC-IMRCs 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.
Details
- Title: Subtitle
- Human embryonic stem cell-derived mesenchymal stem cell secretome reverts silica-induced airway epithelial cell injury by regulating Bmi1 signaling
- Creators
- Jiali Yang - The Fourth People's Hospital of Ningxia Hui Autonomous RegionJing Xue - Ningxia UniversityWenfeng Hu - Ningxia UniversityLifan Zhang - Ningxia UniversityRanran Xu - Zephyrm Biotechnologies Co., Ltd., Beijing, ChinaShuang Wu - Ningxia UniversityJing Wang - The Fourth People's Hospital of Ningxia Hui Autonomous RegionJia Ma - Ningxia UniversityJun Wei - Zephyrm Biotechnologies Co., Ltd., Beijing, ChinaYujiong Wang - Ningxia UniversityShuyan Wang - Zephyrm Biotechnologies Co., Ltd., Beijing, ChinaXiaoming Liu - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Environmental toxicology, Vol.38(9), pp.2084-2099
- DOI
- 10.1002/tox.23833
- PMID
- 37227716
- eISSN
- 1522-7278
- Grant note
- 32260174 / National Natural Science Foundation of China 32070863 / National Natural Science Foundation of China 31860318 / National Natural Science Foundation of China 2022GZRYSY035 / National Natural Science Foundation of China pre-experiment
- Language
- English
- Electronic publication date
- 05/25/2023
- Date published
- 09/2023
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984419357902771
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