Bladder cancer cell in co-culture induces human stem cell differentiation to urothelial cells through paracrine FGF10 signaling

Seyung S. Chung, Chester J. Koh

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Fibroblast growth factor 10 (FGF10) is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of limb bud formation. In this study, we investigated the role of FGF10 as a lead induction factor for stem cell differentiation toward urothelial cell. To this end, human multipotent stem cell in vitro system was employed. Human amniotic fluid stem cells were co-cultured with immortalized bladder cancer lines to induce directed differentiation into urothelial cells. Urothelial markers, uroplakin II, III, and cytokeratin 8, were monitored by RT-PCR, immunocytochemistry, and Western blot analysis. Co-cultured stem cells began to express uroplakin II, III, and cytokeratin 8. Targeted FGF10 gene knockdown from bladder cancer cells abolished the directed differentiation. In addition, when FGF10 downstream signaling was blocked with the Mek inhibitor, the co-culture system lost the capacity to induce urothelial differentiation. Exogenous addition of recombinant FGF10 protein promoted stem cell differentiation into urothelium cell lineage. Together, this report suggests that paracrine FGF10 signaling stimulates the differentiation of human stem cell into urothelial cells. Current study provides insight into the potential role of FGF10 as a lead growth factor for bladder regeneration and its therapeutic application for bladder transplantation.

Original languageEnglish (US)
Pages (from-to)746-751
Number of pages6
JournalIn Vitro Cellular and Developmental Biology - Animal
Volume49
Issue number10
DOIs
StatePublished - Dec 2013

Keywords

  • Bladder cancer cells
  • Co-culture
  • Fibroblast growth factor 10
  • Human amniotic fluid stem cell
  • Urothelium

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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