RRC ID |
69333
|
著者 |
Zhou Q, Ye X, Sun R, Matsumoto Y, Moriyama M, Asano Y, Ajioka Y, Saijo Y.
|
タイトル |
Differentiation of mouse induced pluripotent stem cells into alveolar epithelial cells in vitro for use in vivo.
|
ジャーナル |
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.
|
巻・号 |
3(6)
|
ページ |
675-85
|
公開日 |
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
|
リソース情報 |
ヒト・動物細胞 |
iPS-MEF-Ng-492B-4(APS0004) |