Essential roles of sphingosine-1-phosphate and platelet-derived growth factor in the maintenance of human embryonic stem cells

Stem Cells. 2005 Nov-Dec;23(10):1541-8. doi: 10.1634/stemcells.2004-0338. Epub 2005 Aug 4.


Human embryonic stem cells (hESCs) have great potential for use in research and regenerative medicine, but very little is known about the factors that maintain these cells in the pluripotent state. We investigated the role of three major mitogenic agents present in serum--sphingosine-1-phosphate (S1P), lysophosphatidic acid (LPA), and platelet-derived growth factor (PDGF)--in maintaining hESCs. We show here that although LPA does not affect hESC growth or differentiation, coincubation of S1P and PDGF in a serum-free culture medium successfully maintains hESCs in an undifferentiated state. Our studies indicate that signaling pathways activated by tyrosine kinase receptors act synergistically with those downstream from lysophospholipid receptors to maintain hESCs in the undifferentiated state. This study is the first demonstration of a role for lysophospholipid receptor signaling in the maintenance of stem cell pluri-potentiality.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Cells, Cultured
  • Embryo Research
  • Humans
  • Lysophospholipids / pharmacology
  • Lysophospholipids / physiology*
  • Platelet-Derived Growth Factor / pharmacology
  • Platelet-Derived Growth Factor / physiology*
  • Receptor, Platelet-Derived Growth Factor beta / drug effects
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptors, Lysophosphatidic Acid / drug effects
  • Receptors, Lysophosphatidic Acid / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Sphingosine / physiology
  • Stem Cells / cytology*
  • Stem Cells / physiology*


  • Lysophospholipids
  • Platelet-Derived Growth Factor
  • Receptors, Lysophosphatidic Acid
  • sphingosine 1-phosphate
  • Receptor, Platelet-Derived Growth Factor beta
  • Sphingosine