Noggin and bFGF cooperate to maintain the pluripotency of human embryonic stem cells in the absence of feeder layers.
Human embryonic stem (hES) cells are typically maintained on mouse embryonic fibroblast (MEF) feeders or with MEF-conditioned medium. However, these xenosupport systems greatly limit the therapeutic applications of hES cells because of the risk of cross-transfer of animal pathogens. Here we showed that the bone morphogenetic protein antagonist noggin is critical in preventing differentiation of hES cells in culture. Furthermore, we found that the combination of noggin and basic fibroblast growth factor (bFGF) was sufficient to maintain the prolonged growth of hES cells while retaining all hES cell features. Since both noggin and bFGF are expressed in MEF, our findings suggest that they may be important factors secreted by MEF for maintaining undifferentiated pluripotent hES cells. Our data provide new insight into the mechanism how hES cell self-renewal is regulated. The newly developed feeder-free culture system will provide a more reliable alternative for future therapeutic applications of hES cells.
Wang
Guangwen
G
Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing, China.
Zhang
Hong
H
Zhao
Yang
Y
Li
Jian
J
Cai
Jun
J
Wang
Peigang
P
Meng
Sha
S
Feng
Jingbo
J
Miao
Chenglin
C
Ding
Mingxiao
M
Li
Dongsheng
D
Deng
Hongkui
H
D000818:Animals; D002352:Carrier Proteins; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004338:Drug Combinations; D004622:Embryo, Mammalian / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D007621:Karyotyping; D007797:Laminin; D051379:Mice; D041681:NIH 3T3 Cells; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans; D000099176:Noggin Protein
D002352:Carrier Proteins; D003094:Collagen; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D016222:Fibroblast Growth Factor 2; D007797:Laminin; D011506:Proteins; D011509:Proteoglycans; D000099176:Noggin Protein; C059485:matrigel