Format

Send to

Choose Destination
Stem Cell Reports. 2014 Sep 9;3(3):394-403. doi: 10.1016/j.stemcr.2014.07.005. Epub 2014 Aug 21.

Generation of alveolar epithelial spheroids via isolated progenitor cells from human pluripotent stem cells.

Author information

1
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Electronic address: a0009650@kuhp.kyoto-u.ac.jp.
2
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8507, Japan. Electronic address: isaoito@kuhp.kyoto-u.ac.jp.
3
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
4
Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.
5
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

Abstract

No methods for isolating induced alveolar epithelial progenitor cells (AEPCs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have been reported. Based on a study of the stepwise induction of alveolar epithelial cells (AECs), we identified carboxypeptidase M (CPM) as a surface marker of NKX2-1(+) "ventralized" anterior foregut endoderm cells (VAFECs) in vitro and in fetal human and murine lungs. Using SFTPC-GFP reporter hPSCs and a 3D coculture system with fetal human lung fibroblasts, we showed that CPM(+) cells isolated from VAFECs differentiate into AECs, demonstrating that CPM is a marker of AEPCs. Moreover, 3D coculture differentiation of CPM(+) cells formed spheroids with lamellar-body-like structures and an increased expression of surfactant proteins compared with 2D differentiation. Methods to induce and isolate AEPCs using CPM and consequently generate alveolar epithelial spheroids would aid human pulmonary disease modeling and regenerative medicine.

PMID:
25241738
PMCID:
PMC4266003
DOI:
10.1016/j.stemcr.2014.07.005
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center