We Can Reprogram Skin Cells Into Stem Cells - So Do We Still Need Embryos?

This month we've witnessed the first-time success of two important stem cell research techniques in primate cells. Both techniques were previously developed in mice, but their success in humans and monkeys is important. Stem cells from cloned embryos have been generated from macaque cells. And now this week, two papers (here and here - this last one is a PDF file) have been published that are reporting that adult human skin cells can be reprogrammed to become stem cells. However, do the results of this week's papers mean that we no longer need to get stem cells from embryos? The answer, for now, is a resounding no - reprogrammed skin cells currently have some serious drawbacks that need to be overcome before they can become worth trying in disease treatments.

How do you reprogram a skin cell (in this case, fibroblasts - a very generic, easily handled cell commonly used in labs) to become a stem cell? The key step is to induce 4 genes that produce important master regulators, the transcription factors named Oct3/4, Sox2, Klf4, and c-Myc. These transcription factors are proteins which switch large sets of genes on or off, thus initiating a cascade of genetic signals that enable the fibroblast to transform itself into a stem cell. It's amazing that just these 4 genes can initiate so many substantial changes, but this is a common phenomenon in biology, found even in yeast.

But does this technique now eliminate the need to take stem cells from embryos? Not yet. Contrary to statements by the White house, this research was not a result "the president’s drawing of lines on cloning and embryo use." Without research on embryonic stem cells, we would have had a hard time identifying the role of the 4 transcription factors in the first place. And even with no restrictions on embryo use, researchers would have still tried these important experiments. Science at its best attacks problems using a variety of strategies.

And it's not clear that this technique is going to produce better results in the near future. The process of transferring the 4 regulator genes into fibroblasts involves a type of virus (not a health-threatening virus - it's basically a handy lab tool), which deposits multiple copies of these genes almost at random around the genome. These four genes can end up in good places or bad places in the genome. In bad places, stem cell transplants can develop into cancers, with the c-Myc gene being an especially frequent culprit (it's a gene known to be involved in a variety of cancers). In mice, up to 20% of stem cell recipients develop cancer.

So our ability to manipulate these cells for a useful purpose still lags. We can do a somewhat better job manipulating embryonic stem cells, but in general we have a hard time getting any plutipotent stem cells to produce the exact kind of desired differentiated tissue, such as nerve or heart cells. To improve the process we need to keep working on reprogramming, but we also need to study how stem cells actually work in nature - that is, in embryos.