In Vitro Propagation and Branching Morphogenesis from Single Ureteric Bud Cells

Stem Cell Reports. 2017 Feb 14;8(2):401-416. doi: 10.1016/j.stemcr.2016.12.011. Epub 2017 Jan 12.


A method to maintain and rebuild ureteric bud (UB)-like structures from UB cells in vitro could provide a useful tool for kidney regeneration. We aimed in our present study to establish a serum-free culture system that enables the expansion of UB progenitor cells, i.e., UB tip cells, and reconstruction of UB-like structures. We found that fibroblast growth factors or retinoic acid (RA) was sufficient for the survival of UB cells in serum-free condition, while the proliferation and maintenance of UB tip cells required glial cell-derived neurotrophic factor together with signaling from either WNT-β-catenin pathway or RA. The activation of WNT-β-catenin signaling in UB cells by endogenous WNT proteins required R-spondins. Together with Rho kinase inhibitor, our culture system facilitated the expansion of UB tip cells to form UB-like structures from dispersed single cells. The UB-like structures thus formed retained the original UB characteristics and integrated into the native embryonic kidneys.

Keywords: R-spondin; branching morphogenesis; fibroblast growth factor; kidney progenitor cells; retinoic acid; ureteric bud.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cell Survival / drug effects
  • Fibroblast Growth Factors / metabolism
  • Kidney / cytology*
  • Kidney / embryology*
  • Mice
  • Models, Biological
  • Morphogenesis*
  • Signal Transduction
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Thrombospondins / genetics
  • Thrombospondins / metabolism
  • Tretinoin / pharmacology
  • Wnt Signaling Pathway / drug effects


  • Thrombospondins
  • Tretinoin
  • Fibroblast Growth Factors