PMID- 33899513 OWN - NLM STAT- MEDLINE DCOM- 20220321 LR - 20220531 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 30 IP - 13 DP - 2021 Jul 1 TI - Type 2 Alveolar Epithelial Cells Differentiated from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Mouse Pulmonary Fibrosis Through beta-Catenin-Regulated Cell Apoptosis. PG - 660-670 LID - 10.1089/scd.2020.0208 [doi] AB - 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-beta1), 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. FAU - Liu, Jiang AU - Liu J AD - 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. FAU - Peng, Danyi AU - Peng D AD - Department of Respiratory, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - You, Jingyi AU - You J AD - 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. AD - Department of Respiratory, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Zhou, Ou AU - Zhou O AD - 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. FAU - Qiu, Huijun AU - Qiu H AD - 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. FAU - Hao, Chang AU - Hao C AD - 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. FAU - Chen, Hong AU - Chen H AD - Department of Pediatric, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Haerbin, China. FAU - Fu, Zhou AU - Fu Z AD - 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. AD - Department of Respiratory, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Zou, Lin AU - Zou L AD - 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. AD - Center of Clinical Molecular Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China. AD - Clinical Research Unit, Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210601 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (CTNNB1 protein, mouse) RN - 0 (Catenins) RN - 0 (beta Catenin) SB - IM MH - *Alveolar Epithelial Cells/cytology/metabolism MH - Animals MH - Apoptosis MH - Catenins/metabolism MH - Cell Differentiation MH - Epithelial Cells/metabolism MH - Humans MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells/cytology/metabolism MH - Mice MH - *Pulmonary Fibrosis MH - Umbilical Cord/cytology/metabolism MH - *beta Catenin/biosynthesis/metabolism OTO - NOTNLM OT - alveolar epithelial cell OT - apoptosis OT - human umbilical cord mesenchymal stem cell OT - pulmonary fibrosis OT - beta-catenin EDAT- 2021/04/27 06:00 MHDA- 2022/03/22 06:00 CRDT- 2021/04/26 08:45 PHST- 2021/04/27 06:00 [pubmed] PHST- 2022/03/22 06:00 [medline] PHST- 2021/04/26 08:45 [entrez] AID - 10.1089/scd.2020.0208 [doi] PST - ppublish SO - Stem Cells Dev. 2021 Jul 1;30(13):660-670. doi: 10.1089/scd.2020.0208. Epub 2021 Jun 1.