期刊
STEM CELLS AND DEVELOPMENT
卷 30, 期 13, 页码 660-670出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2020.0208
关键词
human umbilical cord mesenchymal stem cell; alveolar epithelial cell; pulmonary fibrosis; apoptosis; beta-catenin
资金
- National Natural Science Foundation of China [81670018, 81800032]
- Key Grant from Ministry of Science and Technology of China [2016YFA0101302]
- Chongqing Science and Technology Commission
- Chongqing Health Commission [Cstc2014yykfC10003, 2018ZDXM041]
This study demonstrated that intratracheal transplantation of hUC-MSC-derived AEC2s could improve mortality and alleviate fibrosis in bleomycin-induced PF mice through regulating apoptosis mediated by beta-catenin, providing a viable strategy for the treatment of PF.
Pulmonary fibrosis (PF) is a chronic, progressive, and lethal disease with little response to available therapies. One of the major mechanisms of PF is the repeated injury and inadequate regeneration of the alveolar epithelium. In this study, we induced human umbilical cord mesenchymal stem cells (hUC-MSCs) to differentiate into type 2 alveolar epithelial cells (AEC2s), and we provided evidence that intratracheal transplantation of hUC-MSC-derived AEC2s (MSC-AEC2s) could improve mortality and alleviate fibrosis in bleomycin-induced PF mice. Transplantation of MSC-AEC2s could increase the AEC2 cell count in these mice, and the results of the cell tracing experiment exhibited that the increased AEC2s originated from the self-renewal of mouse alveolar epithelium. The AEC2 survival was controlled by the apoptosis of AEC2s via the expression of beta-catenin in PF mice. In in vitro experiments, MSC-AEC2s could alleviate the apoptosis of MLE-12 cells induced by transforming growth factor beta (TGF-beta 1), which could be eliminated by using PRI-724, a beta-catenin inhibitor, suggesting beta-catenin signaling involved in the protection against apoptosis provided by MSC-AEC2s. Our study demonstrated that MSC-AEC2s could protect PF mice through regulating apoptosis mediated by beta-catenin, which provided a viable strategy for the treatment of PF.
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