Caffeine held the key to creating embryonic stem cells from cloned embryos

A colony of human embryonic stem cells, courtesy of Julie Baker at the Stanford University School of Medicine

Scientists at Oregon Health & Science University have achieved what many scientists have been working toward for decades: they’ve created embryonic stem cells from cloned human embryos.

These cells, like the embryonic stem cells that come from embryos donated after in vitro fertilization (IVF) and from reprogrammed skin cells, have the ability to form all the cell types of the body. This is also called being pluripotent (pluri= “many”, potent= “potential”). So, now there are three ways of generating pluripotent stem cells.

There are some subtle differences between the pluripotent stem cells from those different sources, and so far nobody knows what those differences mean in terms of their therapeutic potential. We do know that reprogrammed skin cells (known as iPS cells) have some changes to their DNA compared to normal embryonic stem cells and they also seem to age more quickly. Whether these differences matter when it comes to using the cells in therapies is still not known.

Like iPS cells, this new source of embryonic stem cells would be genetically identical to the patient. That means they are less likely to be rejected by the patient if the cells are used as a therapy, for example transplanted into the brain to treat Parkinson’s disease. But unlike iPS cells, the new source is relatively quick to make – on the order of weeks rather than the months it can take to reprogram skin or other tissues into iPS cells.

A story in Reuters quotes CIRM’s Natalie DeWitt discussing this increased speed:

“If you have a patient who needs [stem-cell-derived tissue], that can be an important difference.”

The story goes on to point out some potential drawbacks to the approach:

On the other hand, the human eggs needed for the Dolly technique are in short supply and hard to obtain, notes MIT’s Jaenisch. (The Oregon team paid the women who donated eggs for their time and “discomfort.”) Although the Oregon team coaxed stem cells out of every egg they collected from one of the women, other labs might not be so efficient.

The process

Many incremental steps have led to this recent advance, which the team published today in the journal Cell. In 2011, a group in New York also created embryonic stem cells through this technique, also called SCNT (somatic cell nuclear transfer) but their cells had three copies of each chromosome, limiting their usefulness. Normal cells have two copies of each chromosome, one from the mother and one from the father. We blogged about that work here.

SCNT is a reprogramming method that involves creating an embryo as a first step. In this case, the scientists first removed the nucleus, containing all the cell’s DNA, from a human egg. They then took DNA from a human skin cell and placed it in the egg, which they then stimulated to form a 5-6 day old embryo. Those embryos are like the 5-6 day old embryos donated through IVF clinics that are normally used to generate embryonic stem cells. Scientists remove cells from those embryos and place them in a lab dish where they go on to form embryonic stem cells.

That same paragraph would have described attempts to create SCNT-derived stem cells a decade ago, so what took so long? There aren’t that many steps. The scientists spent their time making minute tweaks to the cocktail of chemicals bathing the egg to stimulate it to start dividing and forming an embryo. Normally, the egg begins to divide when fertilized by a sperm, but with no sperm involved scientists had to figure out what chemicals could mimic fertilization. It turns out, the key was coffee. Or rather caffeine.

The fact that SCNT-derived stem cell lines have so much in common with other forms of pluripotent stem cells has some opponents of the research asking why bother? Here’s why. CIRM held a conference in June 2010 to discuss the value of pursuing SCNT and posted a report on the findings in November, 2010 (a report from that workshop is here).

That report suggests three areas where embryonic stem cell lines generated through SCNT would clearly be valuable:

  • Understanding how you reprogram any cell to become pluripotent could help us optimize the creation of iPS cells, which are so far inefficient to create in addition to being incompletely reprogrammed.
  • Understanding and treating the rare diseases that are passed on from those few genes that reside outside the nucleus in the cellular organ called the mitochondria.
  • Studying the very early stages of human development, which are poorly understood now, and which is when some human diseases are thought to originate.


This research brings up ethical concerns for many groups. First. SCNT requires woman to donate eggs. The Oregon team paid women for those eggs, which some oppose. In California, both CIRM regulations and state law prohibit any payment to women who donate eggs for research.

Also, there’s the issue of creating a cloned human embryo. In other animals, scientists can implant that embryo into a uterus and produce cloned animals such as Dolly the sheep. In California, that step—called reproductive cloning—is prohibited by a constitutional amendment. All significant research oversight groups oppose human reproductive cloning.

You can learn more about the different types of stem cells used in CIRM-funded research on our website. This table lists all awards, with filters on the left to see which grants use iPS, embryonic, adult, cancer or SCNT cells.

This video shows CIRM grantee Amander Clark from UCLA discussing the process of SCNT:


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