Human Embryonic Stem (ES) Cells from Skin Cells

Adding four genes to a skin cell eliminates the ethical problems of ES cells
Another week, another stem cell story. Two weeks ago scientists in Oregon cloned monkeys. Last week scientists in Japan and Wisconsin made embryonic stem (ES) cells from human skin cells. This last one is a big step in producing ES cells that do not trouble bio-ethicists or pro-lifers. ES cells are special because they can make new copies of themselves forever. And they can turn into any other kind of cell. These two features make ES cells ideal for curing diseases where cells that can't be regrown are destroyed. For example, in Type 1 diabetes the cells of the pancreas that make insulin are destroyed and the body can't make new ones. But scientists in the lab can turn ES cells into these pancreatic cells. The hope is that the scientists can then add these new pancreas cells back to the patient. And so cure diabetes instead of just treating it. Sounds wonderful except there is a catch. To get ES cells, a scientist needs to destroy an embryo. And to get the most useful ES cells, a scientist needs to clone the patient and then destroy an embryo. There are obvious difficulties here for people who think that an embryo is a life. Or for those people worried that some scientist won't stop at a cloned embryo and will instead grow a whole new person. The research that came out last week eliminates these worries. By turning a patient's skin cell into an ES cell, no cloning is required. And no embryo need be destroyed. These ethical stem cells from the patient may open up all sorts of possibilities in personalized medicine.
Turning a Skin Cell into an ES Cell
Two different groups of scientists have turned human skin cells into embryonic stem (ES) cells by adding four genes to a skin cell. These added genes essentially erased the skin cell programming and re-installed the ES programming. To understand why this worked, we need to go a bit deeper into what makes two cell types different. All of our cells have the same DNA. What makes one cell type different from another is which genes are on or off in a particular cell. Remember, that for a gene to have an effect, it has to be on. In essence, this means that a cell can recognize that a particular gene is there. Once the cell recognizes a gene, its machinery can read the instructions and make a specific protein. Proteins do most of the work in a cell and different cell types have different sets of proteins. For example, we don't need proteins that let an eye see to be present in a liver cell. So the eye protein genes are shut off in the liver. What determines if a gene is on or off? Other genes. These genes make proteins that let the cell's machinery see a gene. Or they make proteins that hide a gene. These proteins all work together to program a cell to be a skin cell. Or a muscle cell. Or an ES cell. What the researchers did was add genes that are normally on in an ES cell to a skin cell. These genes made proteins that reprogrammed the skin cell into an ES cell. The researchers knew which genes to add back from previous work the Japanese researchers had done in mice. In fact, a lot of the work done by these two groups is really just a repeat of the previous mouse work in human cells.

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Embryonic stem cells
can become any
other kind of cell.
OK, So What's New?
The first new finding is an obvious one—the mouse experiments worked in human cells. Just because something worked in mice doesn't necessarily mean it will work in people too. So this is a really important finding. The second important finding has to do with the specific genes each group used. Both groups added four genes to turn a stem cell into an ES cell. But they used a slightly different set of genes. The Japanese group added OCT3/4, SOX2, KLF4, and c-MYC. The Wisconsin group added OCT4, SOX2, NANOG, and LIN28. This matters because of a side effect seen in the previous mouse study. The mouse study went farther than the human study in that the researchers added these new ES cells to a mouse embryo. The results were disconcerting. Around 20% of the mice developed cancer from the cells. The researchers hypothesized that the cause was one or more of the genes that were used to create the ES cell. By using different sets of genes in the human cell study, the researchers showed you don't need the same four genes to create an ES cell. The hope is that the researchers will find a combination of genes that do not cause cancer. Once the scientists find a set of genes that don't cause cancer, this research should blow the stem cell field wide open. We still don't know if ES cells will work to actually cure disease. But ethical ES cells should open the spigot of federal funds so American scientists can finally research this subject to its full extent. Then we'll see if ES cells can really live up to their hype. Or if we need to pursue other ways to cure these illnesses.
Four genes, possible
new lease on life.