By Anthony L. Komaroff, M.D.
Brigham and Women's Hospital

Suppose you had a disease that had destroyed cells in your body. Perhaps you had a heart attack that killed some of your heart muscle cells, and you wanted to replace the dead cells with stem cells that had been turned into heart muscle cells.

The type of stem cell that has the greatest capacity to turn into any type of cell in your body is an embryonic stem cell. Ideally, you would want your own embryonic stem cells. Why? Because they are genetically identical to all the rest of your cells, and would not be attacked as "foreign" if they were placed in your body.

However, that isn't possible: your own embryonic stem cells only existed for a very short time, decades ago when you were an embryo in your mother's womb, and you can't turn back the clock.

Or can you? There are now two ways of making cells that — if not identical to what your own embryonic stem cells were like — appear to be very similar.

Nuclear transfer

In animals, a technique called "nuclear transfer" can create an egg that contains an adult animal's genes, and that grows into a clone of the adult animal. An example is the famous sheep "Dolly."

If it could be made to work in a human being like you, how would nuclear transfer work? Here are the steps:

Although nuclear transfer has not been shown to work in human beings, most experts think that it someday will work. But since it involves creating an human embryo, it raises ethical concerns for some people. And it would still be a lot of work: removing an egg from a woman's ovary, inserting new genes into the egg, etc. So scientists began to wonder if something even more amazing might not be possible. Maybe scientists could take one of your specialized cells that was easy to reach, like a skin cell, and "reprogram" it to become an embryonic stem cell — without even putting it in an egg and creating a human embryo!

Reprogramming Cells

In June 2007, several research groups reported that they had been able to transform cells in the skin of adult mice into cells with all the qualities and potential of embryonic stem cells. They accomplished this remarkable feat by inserting four genes into the skin cells — genes that reprogrammed the cell to become an embryonic stem cell. Such cells are called induced pluripotent stem cells, or iPS cells, for short.

Unlike nuclear transfer, this new technique did not involve the creation of an embryo. And it was a lot simpler than nuclear transfer.

Scientists the world over were impressed with this remarkable accomplishment. But many were skeptical about two things:

Could Reprogrammed Cells Really Cure a Disease?

Some scientists questioned if these "reprogrammed" cells that looked like embryonic stem cells in the laboratory dish, would actually be able to cure disease in an animal. After all, that was the promise of stem cell therapy.

But in December 2007, scientists from the Massachusetts Institute of Technology (MIT) reported that they had cured sickle cell anemia in mice by using reprogrammed cells. (Sickle cell disease is caused by a mutation that makes an unhealthy form of hemoglobin called sickle hemoglobin.)

First, the scientists transformed cells from the skin of the tails of the mice into cells like embryonic stem cells, using reprogramming. Then they placed a gene for the healthy form of hemoglobin into these cells. Next, they transformed these cells into blood forming cells. Now they had created cells in the laboratory dish that could form an entirely new blood system in the sick mice.

Then they killed all of the blood cells in the sick mice using irradiation. Now the mice had no sick blood cells, but they also had no blood cells at all! And if they were to survive, they needed healthy new cells. So the scientists transplanted the reprogrammed cells they had created into the mice. These new cells formed a new, healthy blood system and the mice were cured of sickle cell anemia. Cells from their skin had been turned into a new, healthy blood system!

As an encore, the scientists also used reprogrammed cells to cure Parkinson's disease in mice!

Could Reprogrammed Cells Work in Humans?

Some scientists also questioned if the reprogramming of skin cells that had worked in mice could work in humans. Not everything that works in mice works in humans, but the reason scientists study mice — mammals just like us — is that a lot of things that work in mice also work in humans.

In November 2007 — just five months after the remarkable results in mice were announced—two research groups reported that they had made the same technique work in humans.

However, much more research will be required to be sure that it can be done safely. For example, the first experiments creating reprogrammed cells in humans used techniques that increased the risk the cells could turn cancerous. However, since late 2007 other techniques that do not seem to raise the risk of cancer have been successful in reprogramming cells.

No one can predict for sure whether and when this breakthrough will lead to stem cell treatments that will cure suffering and prolong life. It could be a long time.

However, few people imagined that embryonic stem cells could be created from specialized cells under any circumstances — yet it happened. Fewer still imagined that embryonic stem cells could be created from specialized cells without first creating an embryo — yet they can. And when that was accomplished in mice, few people imagined that it could happen just five months later in humans — yet it has.

That is why we think it is likely that the reprogramming of specialized human cells into cells like embryonic stem cells will be regarded as a landmark event — a turning point in the history of human stem cell science and treatment.

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