2. Academic Validation
  3. Type 2 Alveolar Epithelial Cells Differentiated from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Mouse Pulmonary Fibrosis Through β-Catenin-Regulated Cell Apoptosis

Type 2 Alveolar Epithelial Cells Differentiated from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Mouse Pulmonary Fibrosis Through β-Catenin-Regulated Cell Apoptosis

  • Stem Cells Dev. 2021 Jul 1;30(13):660-670. doi: 10.1089/scd.2020.0208.
Jiang Liu 1,  Danyi Peng 2,  Jingyi You 1 2,  Ou Zhou 1,  Huijun Qiu 1,  Chang Hao 1,  Hong Chen 3,  Zhou Fu 1 2,  Lin Zou 1 4 5
Affiliations

Affiliations

  • 1 Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing Engineering Research Center of Stem Cell Therapy; Children's Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Respiratory, Children's Hospital of Chongqing Medical University, Chongqing, China.
  • 3 Department of Pediatric, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Haerbin, China.
  • 4 Center of Clinical Molecular Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China.
  • 5 Clinical Research Unit, Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
PMID: 33899513 DOI: 10.1089/scd.2020.0208
Abstract

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 β-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-β1), which could be eliminated by using PRI-724, a β-catenin Inhibitor, suggesting β-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 β-catenin, which provided a viable strategy for the treatment of PF.

Keywords

alveolar epithelial cell; apoptosis; human umbilical cord mesenchymal stem cell; pulmonary fibrosis; β-catenin.

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