Indole derivatives sustain embryonic stem cell self-renewal in long-term culture

Biosci Biotechnol Biochem. 2008 May;72(5):1242-8. doi: 10.1271/bbb.70717. Epub 2008 May 7.

Abstract

Embryonic stem cells (ESCs), which have characteristics such as self-renewal, indefinite proliferation, and pluripotency, are thought to hold great promise for regenerative medicine. ESCs are generally cultured on mouse embryonic fibroblast (MEF) or MEF conditioned medium (MEF-CM). However, for therapeutic applications, it is preferable for ESCs to be cultured under chemically defined conditions. Here, we report synthetic compounds that allow expansion of undifferentiated mouse ESCs in the absence of MEF, Leukemia Inhibitory Factor (LIF), and Fetal Bovine Serum (FBS). ESCs cultured for more than 30 d in a serum-free medium supplemented with indole derivertives retained their characteristic morphology and expressed markers such as SSEA-1, OCT3/4, Rex-1, Sox2, and Nanog. They consistently differentiated into many types of cells, including neurons, muscle cells, and hepatocytes. These results indicate that our compounds provide a more efficient and safer large-scale culture system for pluripotent ESCs, and hence might contribute to the use of ESCs in therapeutic applications.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Culture Media, Serum-Free
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / drug effects*
  • Embryonic Stem Cells / metabolism
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Mice
  • Organic Cation Transport Proteins / genetics
  • Regeneration
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Time Factors

Substances

  • Culture Media, Serum-Free
  • Indoles
  • Organic Cation Transport Proteins
  • Small Molecule Libraries
  • solute carrier family 22 (organic cation transporter), member 3
  • indole
  • Alkaline Phosphatase