RRC ID 34789
著者 Yoshida S, Yasuda M, Miyashita H, Ogawa Y, Yoshida T, Matsuzaki Y, Tsubota K, Okano H, Shimmura S.
タイトル Generation of stratified squamous epithelial progenitor cells from mouse induced pluripotent stem cells.
ジャーナル PLoS One
Abstract BACKGROUND:Application of induced pluripotent stem (iPS) cells in regenerative medicine will bypass ethical issues associated with use of embryonic stem cells. In addition, patient-specific IPS cells can be useful to elucidate the pathophysiology of genetic disorders, drug screening, and tailor-made medicine. However, in order to apply iPS cells to mitotic tissue, induction of tissue stem cells that give rise to progeny of the target organ is required.
METHODOLOGY/PRINCIPAL FINDINGS:We induced stratified epithelial cells from mouse iPS cells by co-culture with PA6 feeder cells (SDIA-method) with use of BMP4. Clusters of cells positive for the differentiation markers KRT1 or KRT12 were observed in KRT14-positive colonies. We successfully cloned KRT14 and p63 double-positive stratified epithelial progenitor cells from iPS-derived epithelial cells, which formed stratified epithelial sheets consisting of five- to six-polarized epithelial cells in vitro. When these clonal cells were cultured on denuded mouse corneas, a robust stratified epithelial layer was observed with physiological cell polarity including high levels of E-cadherin, p63 and K15 expression in the basal layer and ZO-1 in the superficial layer, recapitulating the apico-basal polarity of the epithelium in vivo.
CONCLUSIONS/SIGNIFICANCE:These results suggest that KRT14 and p63 double-positive epithelial progenitor cells can be cloned from iPS cells in order to produce polarized multilayer epithelial cell sheets.
巻・号 6(12)
ページ e28856
公開日 2011-1-1
DOI 10.1371/journal.pone.0028856
PII PONE-D-11-13236
PMID 22174914
PMC PMC3235161
MeSH Animals Bone Morphogenetic Protein 4 / pharmacology Cell Culture Techniques / methods* Cell Differentiation / drug effects Cell Proliferation / drug effects Cells, Cultured Clone Cells Cornea / cytology Epidermal Cells Epidermis / drug effects Epidermis / metabolism Epithelial Cells / cytology* Epithelial Cells / drug effects Epithelial Cells / ultrastructure Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / drug effects Induced Pluripotent Stem Cells / metabolism Mice Stem Cells / cytology* Stem Cells / drug effects Stem Cells / metabolism Time Factors Tissue Engineering
IF 2.74
引用数 18
WOS 分野 CELL BIOLOGY
リソース情報
遺伝子材料 CSII-EF-mRFP1 (RDB06387)