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First published online August 4, 2005
Stem Cells Vol. 23 No. 10 November 2005, pp. 1541 -1548
doi:10.1634/stemcells.2004-0338; www.StemCells.com
© 2005 AlphaMed Press

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Essential Roles of Sphingosine-1-Phosphate and Platelet-Derived Growth Factor in the Maintenance of Human Embryonic Stem Cells

Alice Pébaya, Raymond C.B. Wonga, Stuart M. Pitsonb, Ernst J. Wolvetanga, Gary S.-L. Peha, Adam Filipczyka, Karen L.L. Koha, Irene Tellisa, Linh T.V. Nguyena, Martin F. Peraa

a Monash Institute of Medical Research, Laboratory of Embryonic Stem Cell Biology, Australian Stem Cell Centre, Monash University, Clayton, Australia;
b Hanson Institute, Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, Australia

Key Words. Human embryonic stem cells • Sphingosine-1-phosphate • Platelet-derived growth factor • Lysophosphatidic acid

Correspondence: Alice Pébay, Ph.D., Monash Institute of Medical Research, Laboratory of Embryonic Stem Cell Biology, Australian Stem Cell Centre, Building 75, STRIP Monash University, Wellington Road, Clayton VIC 3800, Australia. Telephone: 61-39-271-1143; Fax: 61-9271-1198; e-mail: alice.pebay{at}med.monash.edu.au

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.




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