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Cell and Tissue Research

, Volume 347, Issue 3, pp 737–746 | Cite as

Transdifferentiation of human adipose-derived stem cells into urothelial cells: potential for urinary tract tissue engineering

  • Jian-Guo Shi
  • Wei-Jun FuEmail author
  • Xiao-Xiong Wang
  • Yong-De Xu
  • Gang Li
  • Bao-Fa Hong
  • Kun Hu
  • Fu-Zhai Cui
  • Yan Wang
  • Xu Zhang
Regular Article

Abstract

Autologous urothelial cells (UCs) provide a cell source for urinary tissue engineering because they can be used safely due to their lack of immunogenicity. However, these cells cannot be harvested under the following circumstances: malignancy, infection and organ loss, etc. Human adipose-derived stem cells (HADSCs) possess the traits of high differentiation potential and ease of isolation, representing a promising resource for tissue engineering and regenerative medicine. Nevertheless, HADSCs have been poorly investigated in urology and the optimal approaches to induce HADSCs into urothelium are still under investigation. In this study, we hypothesized that the change of microenvironment by a conditioned medium was essential for the transdifferentiation of HADSCs into UCs. We then used a conditioned medium derived from urothelium to alternate the microenvironment of HADSCs. After 14 days of culture in a conditioned medium, about 25–50% HADSCs changed their morphology into polygonal epithelium-like shapes. In addition, these cells expressed up-regulating of urothelial lineage-specific markers (uroplakin 2and cytokeratin-18) and down-regulating of mesenchymal marker (vimentin) in RNA and protein level, respectively, which confirmed that HADSCs were induced into urothelial lineage cells. We also measured the growth factors in the conditioned medium in order to analyze the molecular mechanisms regulating transdifferentiation. We observed that the expression levels of PDGF-BB and VEGF were significantly higher than those of the control group after 14 days induction, suggesting they were abundantly secreted into the medium during the culturing period. In conclusion, HADSCs showed in vitro the upregulation of markers for differentiation towards urothelial cells by culturing in an urothelial-conditioned medium, which provides an alternative cell source for potential use in urinary tract tissue engineering.

Keywords

Human adipose-derived stem cells Transdifferentiation Urothelial cells Urinary tract Tissue engineering 

Notes

Acknowledgements

This study was supported by the National Natural Science Foundation (No. 81070555), Beijing Natural Foundation (No.2092029) and the Major Project of Clinical High and New Technology of Army hospital.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Jian-Guo Shi
    • 1
  • Wei-Jun Fu
    • 1
    Email author
  • Xiao-Xiong Wang
    • 1
  • Yong-De Xu
    • 1
  • Gang Li
    • 1
  • Bao-Fa Hong
    • 1
  • Kun Hu
    • 2
  • Fu-Zhai Cui
    • 2
  • Yan Wang
    • 3
  • Xu Zhang
    • 1
  1. 1.Department of Urology, Chinese People’s Liberation Army General HospitalMilitary Postgraduate Medical CollegeBeijingPeople’s Republic of China
  2. 2.Biomaterials Lab, School of Materials Science and EngineeringTsinghua UniversityBeijingPeople’s Republic of China
  3. 3.Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research CenterAcademy of Military Medical SciencesBeijingPeople’s Republic of China

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