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Original Article |
1 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
2 Hanson Institute, Division of Human Immunology, Institute of Medical and Veterinary Science, Frome Road, Adelaide SA 5000, Australia
* To whom correspondence should be addressed. E-mail: alice.pebay{at}med.monash.edu.au.
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Abstract |
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Human embryonic stem cells (HESC) have great potential for use in research and regenerative medicine, but very little is known of 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 HESC. We show here that while LPA does not affect HESC growth or differentiation, co-incubation of S1P and PDGF in a serum-free culture medium successfully maintains HESC in an undifferentiated state. Our studies indicate that signalling pathways activated by tyrosine kinase receptors act synergistically with those downstream from lysophospholipid (LPL) receptors to maintain HESC in the undifferentiated state. This study is the first demonstration of a role for LPL receptor signalling in the maintenance of stem cell pluripotentiality.
Key Words. human embryonic stem cells, sphingosine-1-phosphate, platelet-derived growth factor, lysophosphatidic acid
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