Melton emphasized that the choice of growth factors was a practical one and by no means represents the broad spectrum of growth factors that might govern stem cell differentiation. "While we have demonstrated the potential for directing the differentiation of these cells for use in cell replacement therapy, even in the best case, this represents only an initial step forward," he said. "Besides choosing those growth factors that were available, we chose those for which we could detect receptors on the surface of the cells. There was no sense in adding a growth factor if the cells didn't express a receptor for that growth factor."
The growth factors directed the stem cells to differentiate into three different categoriesendodermal, ectodermal and mesodermal. Endodermal cells give rise to the liver and pancreas; ectodermal cells become brain, skin and adrenal tissues; and mesodermal cells become muscle. Furthermore, the researchers found that they could categorize the growth factors based on their effects on differentiation. One group of growth factors appeared to inhibit endodermal and ectodermal cells, but allowed differentiation into mesodermal cells. A second group induced differentiation into ectodermal and mesodermal cells, and a third group allowed differentiation into all three embryonic lineages.
"When an egg cell divides, it doesn't immediately tell its daughter cells to become nerve, brain or pancreatic cells," said Melton. "Rather, it first parses cells into the three general territories (germ layers)ectoderm, mesoderm and endoderm. And, our studies showed that the growth factors encourage cells to develop into more of one germ layer and less of the other two.
"In the best of all possible worlds, one would like to find growth factors could be added to a human embryonic stem cell to make it become a cardiomyocyte to replace defective heart muscle or a pancreatic beta cell for transplantation into diabetics," s
Contact: Jim Keeley
Howard Hughes Medical Institute