Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells

PLoS One. 2013 Jun 3;8(6):e64843. doi: 10.1371/journal.pone.0064843. Print 2014.

Abstract

Embryonic stem cells and induced pluripotent stem cells have the ability to differentiate into various organs and tissues, and are regarded as new tools for the elucidation of disease mechanisms as well as sources for regenerative therapies. However, a method of inducing organ-specific cells from pluripotent stem cells is urgently needed. Although many scientists have been developing methods to induce various organ-specific cells from pluripotent stem cells, renal lineage cells have yet to be induced in vitro because of the complexity of kidney structures and the diversity of kidney-component cells. Here, we describe a method of inducing renal tubular cells from mouse embryonic stem cells via the cell purification of kidney specific protein (KSP)-positive cells using an anti-KSP antibody. The global gene expression profiles of KSP-positive cells derived from ES cells exhibited characteristics similar to those of cells in the developing kidney, and KSP-positive cells had the capacity to form tubular structures resembling renal tubular cells when grown in a 3D culture in Matrigel. Moreover, our results indicated that KSP-positive cells acquired the characteristics of each segment of renal tubular cells through tubular formation when stimulated with Wnt4. This method is an important step toward kidney disease research using pluripotent stem cells, and the development of kidney regeneration therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Cadherins / chemistry
  • Cadherins / metabolism*
  • Cell Differentiation* / drug effects
  • Collagen / pharmacology
  • Drug Combinations
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Extracellular Space / chemistry
  • Hepatocyte Growth Factor / pharmacology
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / pharmacology
  • Kidney Tubules / cytology*
  • Kidney Tubules / embryology
  • Kidney Tubules / ultrastructure
  • Laminin / pharmacology
  • Mice
  • NIH 3T3 Cells
  • Organ Specificity / drug effects
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / metabolism*
  • Proteoglycans / pharmacology
  • Wnt4 Protein / pharmacology

Substances

  • Antibodies, Monoclonal
  • Cadherins
  • Cdh16 protein, mouse
  • Drug Combinations
  • Laminin
  • Proteins
  • Proteoglycans
  • Wnt4 Protein
  • matrigel
  • Hepatocyte Growth Factor
  • Insulin-Like Growth Factor I
  • Collagen

Grant support

This work was supported in part by Grant-in-Aid for Scientific Research (KAKENHI, 23890203, 21591038, 24591211) and a grant from Daiwa Securities Health Foundation (http://www.daiwa-grp.jp/dsh/index.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.