Special Harvard Commentary: Making Embryonic Stem Cells

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Special Harvard Commentary: Making Embryonic Stem Cells
Reviewed by the Faculty of Harvard Medical School

Special Harvard Commentary: Making Embryonic Stem Cells

Special Harvard Commentary: Making Embryonic Stem Cells

Last reviewed and revised on May 20, 2013

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 your own embryonic stem cells — 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. That egg can then start dividing and grow into an early embryo. From that embryo, embryonic stem cells can be extracted. Those cells are virtually identical to the cells of the adult animal.

In May 2013, scientists reported that this technique also can work in humans. This opens the possibility that nuclear transfer could someday be used to create new cells for a person who suffered from a disease that had killed cells.

Here's how it would work, if you were that person:

  1. An unfertilized egg would be taken from a woman during a minor surgical procedure.
  2. The nucleus in the center of the egg that contains the woman's genes would be extracted.
  3. The nucleus of one of your own cells, with all of your genes, would be inserted into the egg. Now the egg would have a new nucleus, containing your genes.
  4. The egg would double, and the cells keep doubling, until a ball-shaped blastocyst containing embryonic stem cells with your genes was formed.
  5. Embryonic stem cells would be removed from the blastocyst, and then grown in the laboratory. In a few months, there would be millions of embryonic stem cells.
  6. These cells would be like your own embryonic stem cells, with your genes in them. For that reason, theoretically they should not be rejected by your immune system.
  7. Those cells could then be turned into the types of cells that you needed, to replace the cells that had been killed by a disease.

But since it involves creating a human embryo, the technique of nuclear transfer raises ethical concerns for some people.

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. Indeed, the discovery was honored with the Nobel Prize in Medicine in 2012.

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Anthony L. Komaroff, M.D., is professor of medicine and editor-in-chief of Harvard Health Publications at Harvard Medical School. Dr. Komaroff also is senior physician and was formerly director of the Division of General Medicine at Brigham and Women's Hospital. Dr. Komaroff has served on various advisory committees to the federal government, and is an elected Fellow of the American Association for the Advancement of Science.

 

Last updated May 20, 2013


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