RRC ID 69333
Author Zhou Q, Ye X, Sun R, Matsumoto Y, Moriyama M, Asano Y, Ajioka Y, Saijo Y.
Title Differentiation of mouse induced pluripotent stem cells into alveolar epithelial cells in vitro for use in vivo.
Journal Stem Cells Transl Med
Abstract Alveolar epithelial cells (AECs) differentiated from induced pluripotent stem cells (iPSCs) represent new opportunities in lung tissue engineering and cell therapy. In this study, we modified a two-step protocol for embryonic stem cells that resulted in a yield of ∼9% surfactant protein C (SPC)(+) alveolar epithelial type II (AEC II) cells from mouse iPSCs in a 12-day period. The differentiated iPSCs showed morphological characteristics similar to those of AEC II cells. When differentiated iPSCs were seeded and cultured in a decellularized mouse lung scaffold, the cells reformed an alveolar structure and expressed SPC or T1α protein (markers of AEC II or AEC I cells, respectively). Finally, the differentiated iPSCs were instilled intratracheally into a bleomycin-induced mouse acute lung injury model. The transplanted cells integrated into the lung alveolar structure and expressed SPC and T1α. Significantly reduced lung inflammation and decreased collagen deposition were observed following differentiated iPSC transplantation. In conclusion, we report a simple and rapid protocol for in vitro differentiation of mouse iPSCs into AECs. Differentiated iPSCs show potential for regenerating three-dimensional alveolar lung structure and can be used to abrogate lung injury.
Volume 3(6)
Pages 675-85
Published 2014-6-1
DOI 10.5966/sctm.2013-0142
PII sctm.2013-0142
PMID 24763685
PMC PMC4039451
MeSH Alveolar Epithelial Cells / metabolism Alveolar Epithelial Cells / pathology Alveolar Epithelial Cells / transplantation* Animals Biomarkers / metabolism Bleomycin Cell Differentiation* / genetics Cell Line Disease Models, Animal Female Gene Expression Regulation, Developmental Induced Pluripotent Stem Cells / metabolism Induced Pluripotent Stem Cells / transplantation* Intercellular Signaling Peptides and Proteins Mice Mice, Inbred C57BL Peptides / metabolism Phenotype Pulmonary Alveoli / metabolism Pulmonary Alveoli / pathology Pulmonary Alveoli / physiopathology Pulmonary Alveoli / surgery* Pulmonary Fibrosis / chemically induced Pulmonary Fibrosis / genetics Pulmonary Fibrosis / pathology Pulmonary Fibrosis / physiopathology Pulmonary Fibrosis / surgery* Pulmonary Surfactant-Associated Protein C RNA, Messenger / metabolism Regeneration* Time Factors Tissue Scaffolds
IF 6.429
Human and Animal Cells iPS-MEF-Ng-492B-4(APS0004)