TY - JOUR
T1 - Albumin-associated lipids regulate human embryonic stem cell self-renewal
AU - Garcia-Gonzalo, Francesc R.
AU - Belmonte, Juan Carlos Izpisúa
PY - 2008/1/2
Y1 - 2008/1/2
N2 - Background. 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. Methodology/Principal Findings. 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. Conclusions/Significance. 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 extracelldlar factors and has important applications in the development of increasingly chemically defined hESC culture systems.
AB - Background. 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. Methodology/Principal Findings. 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. Conclusions/Significance. 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 extracelldlar factors and has important applications in the development of increasingly chemically defined hESC culture systems.
UR - http://www.scopus.com/inward/record.url?scp=38949201957&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0001384
DO - 10.1371/journal.pone.0001384
M3 - Article
C2 - 18167543
AN - SCOPUS:38949201957
SN - 1932-6203
VL - 3
JO - PloS one
JF - PloS one
IS - 1
M1 - e1384
ER -