Howard Green--who created the technique for culturing sheets of skin in vitro for transplant--and his colleagues at Harvard University set out to turn embryonic stem cells into keratinocytes and then isolate them. Unfortunately, it proved difficult to coax the stem cells to become skin cells in the first place. And those that did convert, Green says, grew poorly compared to donor skin cells.
In fact, the stem cells proved so deficient that the doctors had to introduce genetic material from the human papillomavirus (the virus responsible for cervical cancer) to induce enough keratinocyte growth. With that extra genetic material, the stem cell-derived skin cells proliferated; one line even produced the kind of connected sheet of cells familiar from Green's earlier work with skin grafts according to the findings published in the current online edition of the Proceedings of the National Academies of Science.
Although the stem cell-derived keratinocytes showed all the markings of such skin cells, such as the various proteins typically found in such cells (see image), they did not behave exactly like normal skin cells. Among other things, the stem-cell derived skin cells refused to differentiate in the same way as normal skin cells, Green explains. "It is commonly assumed that the cell types that people seek from stem cells are identical with what they're familiar with from studies of [adult] material," he says. "This is not the case for keratinocytes and may not be the case for other types."
This--plus the fact that the keratinocytes could only be cultured with a viral gene that could pose risks--means that such stem cell-derived skin cells are unlikely to be used anytime soon for skin grafts. And fulfilling the promise of embryonic stem cells may face even more challenges than heretofore imagined. "[Stem cells] are extremely interesting and powerful," Green adds. "We just have to keep working to see what will be the best applications."