Researchers report that they have found a new growth factor that can not only support growth of human embryonic stem cells (hESCs) in vitro but also maintains them in a nearly 100% undifferentiated state without the need for fibroblast feeder cells.
They discovered that cell surface protein Mucin 1 (MUC1) is in an altered form, MUC1*, on pluripotent embryonic stem cells but returns to its normal form when the stem cells begin to differentiate. The team thus suggests that this receptor is an essential switch in the process of cell differentiation.
By adding the growth factor that binds to MUC1*, the investigators say that they were able to expand the hESCs and maintain pluripotency essentially indefinitely.
Furthermore, simply removing the factor triggered cell differentiation.
The team used three antibodies to probe the expression of MUC1 on hESCs: two that recognize the full-length protein (MUC1-FL) and one that recognizes the cleavage product, MUC1*.
The group found that newly differentiated cells no longer expressed the cleaved form, MUC1*, or its ligand, NM23. Instead, they exclusively presented full-length MUC1.
Scientists also discovered that antibody-induced dimerization of the MUC1* receptor on hESCs stimulated cell growth to a far greater degree than currently used methods that require the addition of exogenous basic fibroblast growth factor (bFGF) as well as factors secreted by fibroblast feeder cells.
In an article published earlier this year, the group reported that MUC1 exists in the same altered form, MUC1*, on over 75% of human cancers. Furthermore, the evidence indicated that MUC1* functions as a growth factor receptor on tumor cells while the full-length protein appeared to have no growth promoting activity.
Those results coupled with the most recent findings on MUC1*’s role in hESC differentiation supports the theory that cancer may be caused by a stem cell mechanism gone awry, the scientists say.
The stem cell study, which appears in the October 3 edition of PLoS ONE , was done by researchers from Minerva Biotechnologies and the University of California at Santa Barbara.