Generation of Bladder Urothelium from Human Pluripotent Stem Cells under Chemically Defined Serum- and Feeder-Free System

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Human stem cells are promising sources for bladder regeneration. Among several possible sources, pluripotent stem cells are the most fascinating because they can differentiate into any cell type, and proliferate limitlessly in vitro. Here, we developed a protocol for differentiation of human pluripotent stem cells (hPSCs) into bladder urothelial cells (BUCs) under a chemically defined culture system. We first differentiated hPSCs into definitive endoderm (DE), and further specified DE cells into BUCs by treating retinoic acid under a keratinocyte-specific serum free medium. hPSC-derived DE cells showed significantly expressed DE-specific genes, but did not express mesodermal or ectodermal genes. After DE cells were specified into BUCs, they notably expressed urothelium-specific genes such as UPIb, UPII, UPIIIa, P63 and CK7. Immunocytochemistry showed that BUCs expressed UPII, CK8/18 and P63 as well as tight junction molecules, E-CADHERIN and ZO-1. Additionally, hPSCs-derived BUCs exhibited low permeability in a FITC-dextran permeability assay, indicating BUCs possessed the functional units of barrier on their surfaces. However, BUCs did not express the marker genes of other endodermal lineage cells (intestine and liver) as well as mesodermal or ectodermal lineage cells. In summary, we sequentially differentiated hPSCs into DE and BUCs in a serum- and feeder-free condition. Our differentiation protocol will be useful for producing cells for bladder regeneration and studying normal and pathological development of the human bladder urothelium in vitro.
Publisher
MDPI AG
Issue Date
2014-05
Language
English
Article Type
Article
Keywords

REGENERATIVE MEDICINE; URINARY-BLADDER; IN-VITRO; EFFICIENT DIFFERENTIATION; TISSUE REGENERATION; EXTERNAL GENITALIA; TRACT; AUGMENTATION; INDUCTION; THERAPY

Citation

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.15, no.5, pp.7139 - 7157

ISSN
1422-0067
DOI
10.3390/ijms15057139
URI
http://hdl.handle.net/10203/192714
Appears in Collection
BS-Journal Papers(저널논문)
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