Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium

Abstract For augmentation or reconstruction of urinary bladder after cystectomy, bladder urothelium derived from human induced pluripotent stem cells (hiPSCs) has recently received focus. However, previous studies have only shown the emergence of cells expressing some urothelial markers among deriva...

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Autores principales:	Kotaro Suzuki, Michiyo Koyanagi-Aoi, Keiichiro Uehara, Nobuyuki Hinata, Masato Fujisawa, Takashi Aoi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ecd9f4f3ceb4aacaeb2a6f812908f88
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spelling	oai:doaj.org-article:3ecd9f4f3ceb4aacaeb2a6f812908f882021-12-02T15:09:14ZDirected differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium10.1038/s41598-019-46848-82045-2322https://doaj.org/article/3ecd9f4f3ceb4aacaeb2a6f812908f882019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46848-8https://doaj.org/toc/2045-2322Abstract For augmentation or reconstruction of urinary bladder after cystectomy, bladder urothelium derived from human induced pluripotent stem cells (hiPSCs) has recently received focus. However, previous studies have only shown the emergence of cells expressing some urothelial markers among derivatives of hiPSCs, and no report has demonstrated the stratified structure, which is a particularly important attribute of the barrier function of mature bladder urothelium. In present study, we developed a method for the directed differentiation of hiPSCs into mature stratified bladder urothelium. The caudal hindgut, from which the bladder urothelium develops, was predominantly induced via the high-dose administration of CHIR99021 during definitive endoderm induction, and this treatment subsequently increased the expressions of uroplakins. Terminal differentiation, characterized by the increased expression of uroplakins, CK13, and CK20, was induced with the combination of Troglitazone + PD153035. FGF10 enhanced the expression of uroplakins and the stratification of the epithelium, and the transwell culture system further enhanced such stratification. Furthermore, the barrier function of our urothelium was demonstrated by a permeability assay using FITC-dextran. According to an immunohistological analysis, the stratified uroplakin II-positive epithelium was observed in the transwells. This method might be useful in the field of regenerative medicine of the bladder.Kotaro SuzukiMichiyo Koyanagi-AoiKeiichiro UeharaNobuyuki HinataMasato FujisawaTakashi AoiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kotaro Suzuki Michiyo Koyanagi-Aoi Keiichiro Uehara Nobuyuki Hinata Masato Fujisawa Takashi Aoi Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium
description	Abstract For augmentation or reconstruction of urinary bladder after cystectomy, bladder urothelium derived from human induced pluripotent stem cells (hiPSCs) has recently received focus. However, previous studies have only shown the emergence of cells expressing some urothelial markers among derivatives of hiPSCs, and no report has demonstrated the stratified structure, which is a particularly important attribute of the barrier function of mature bladder urothelium. In present study, we developed a method for the directed differentiation of hiPSCs into mature stratified bladder urothelium. The caudal hindgut, from which the bladder urothelium develops, was predominantly induced via the high-dose administration of CHIR99021 during definitive endoderm induction, and this treatment subsequently increased the expressions of uroplakins. Terminal differentiation, characterized by the increased expression of uroplakins, CK13, and CK20, was induced with the combination of Troglitazone + PD153035. FGF10 enhanced the expression of uroplakins and the stratification of the epithelium, and the transwell culture system further enhanced such stratification. Furthermore, the barrier function of our urothelium was demonstrated by a permeability assay using FITC-dextran. According to an immunohistological analysis, the stratified uroplakin II-positive epithelium was observed in the transwells. This method might be useful in the field of regenerative medicine of the bladder.
format	article
author	Kotaro Suzuki Michiyo Koyanagi-Aoi Keiichiro Uehara Nobuyuki Hinata Masato Fujisawa Takashi Aoi
author_facet	Kotaro Suzuki Michiyo Koyanagi-Aoi Keiichiro Uehara Nobuyuki Hinata Masato Fujisawa Takashi Aoi
author_sort	Kotaro Suzuki
title	Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium
title_short	Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium
title_full	Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium
title_fullStr	Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium
title_full_unstemmed	Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium
title_sort	directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/3ecd9f4f3ceb4aacaeb2a6f812908f88
work_keys_str_mv	AT kotarosuzuki directeddifferentiationofhumaninducedpluripotentstemcellsintomaturestratifiedbladderurothelium AT michiyokoyanagiaoi directeddifferentiationofhumaninducedpluripotentstemcellsintomaturestratifiedbladderurothelium AT keiichirouehara directeddifferentiationofhumaninducedpluripotentstemcellsintomaturestratifiedbladderurothelium AT nobuyukihinata directeddifferentiationofhumaninducedpluripotentstemcellsintomaturestratifiedbladderurothelium AT masatofujisawa directeddifferentiationofhumaninducedpluripotentstemcellsintomaturestratifiedbladderurothelium AT takashiaoi directeddifferentiationofhumaninducedpluripotentstemcellsintomaturestratifiedbladderurothelium
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Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium

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