Differentiation of mouse induced pluripotent stem cells into alveolar epithelial cells in vitro for use in vivo.
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.
Department of Medical Oncology and Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Pediatric Hematology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Department of Neuroanatomy, Cell Biology, and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Qiliang
Q
Zhou
Department of Medical Oncology and Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Pediatric Hematology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Department of Neuroanatomy, Cell Biology, and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Xulu
X
Ye
Department of Medical Oncology and Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Pediatric Hematology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Department of Neuroanatomy, Cell Biology, and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Ruowen
R
Sun
Department of Medical Oncology and Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Pediatric Hematology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Department of Neuroanatomy, Cell Biology, and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Yoshifumi
Y
Matsumoto
Department of Medical Oncology and Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Pediatric Hematology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Department of Neuroanatomy, Cell Biology, and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Masato
M
Moriyama
Department of Medical Oncology and Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Pediatric Hematology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Department of Neuroanatomy, Cell Biology, and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Yoshiya
Y
Asano
Department of Medical Oncology and Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Pediatric Hematology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Department of Neuroanatomy, Cell Biology, and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Yoichi
Y
Ajioka
Department of Medical Oncology and Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Pediatric Hematology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Department of Neuroanatomy, Cell Biology, and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan yasosj@med.niigata-u.ac.jp.
Yasuo
Y
Saijo
D056809:Alveolar Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001761:Bleomycin; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration; D013997:Time Factors; D054457:Tissue Scaffolds
D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger; C489680:Sftpc protein, mouse; D001761:Bleomycin
Differentiation; Induced pluripotent stem cells; Lung; Stem cell transplantation