Details

Autor(en) / Beteiligte

• Garcia-Gonzalo, Francesc R
• Izpisúa Belmonte, Juan Carlos
• Rutherford, Suzannah

Titel

Albumin-associated lipids regulate human embryonic stem cell self-renewal

Ist Teil von

• PloS one, 2008-01, Vol.3 (1), p.e1384-e1384

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2008

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Although human embryonic stem cells (hESCs) hold great promise as a source of differentiated cells to treat several human diseases, many obstacles still need to be surmounted before this can become a reality. First among these, a robust chemically-defined system to expand hESCs in culture is still unavailable despite recent advances in the understanding of factors controlling hESC self-renewal. In this study, we attempted to find new molecules that stimulate long term hESC self-renewal. In order to do this, we started from the observation that a commercially available serum replacement product has a strong positive effect on the expansion of undifferentiated hESCs when added to a previously reported chemically-defined medium. Subsequent experiments demonstrated that the active ingredient within the serum replacement is lipid-rich albumin. Furthermore, we show that this activity is trypsin-resistant, strongly suggesting that lipids and not albumin are responsible for the effect. Consistent with this, lipid-poor albumin shows no detectable activity. Finally, we identified the major lipids bound to the lipid-rich albumin and tested several lipid candidates for the effect. Our discovery of the role played by albumin-associated lipids in stimulating hESC self-renewal constitutes a significant advance in the knowledge of how hESC pluripotency is maintained by extracellular factors and has important applications in the development of increasingly chemically defined hESC culture systems.