Thomson strikes note of caution at World Stem Cell Summit

Joe Vanden Plas

September 22, 2008

Madison, Wis. - James Thomson acknowledged that scientists are notoriously bad at predicting timelines, so when he was asked about the timing of potential therapeutic stem cell research breakthroughs at the World Stem Cell Summit, he was naturally cautious.

Thomson, speaking on the potential future benefits of induced pluripotent stem cells, has been more cautious than some stem cell research advocates when addressing its possibilities. It's not that he isn't enthusiastic about the potential of the research he ignited 10 years ago when he became the first scientist to isolate and develop methods to culture human embryonic stem cells, but he has no illusions about the degree of difficulty that lies ahead.

In developing the induced pluripotent stem cell technique, Thomson and other researchers reprogrammed human adult skin cells to act as human embryonic stem cells. The iPS cells are remarkably similar to human embryonic stem cells in that researchers can make as many of them as they want, and they can become any type of cell in the human body.

Thomson would not be surprised if successful stem cell therapies develop in five to 10 years, but he said they will be few and far between, and there will be many setbacks that the public should be prepared for.

“We need to roll up our sleeves and do a great deal of work here,” he said, “but it's not going to happen

Cell transplantation

Perhaps nowhere is this truer than with transplants. Thomson said both human embryonic stem cells and iPS cells could provide an unlimited source of cells for transplantation therapies. This is the area of stem cell research that has created the most interest, and the one Thomson is most cautious about.

There are several potential barriers to cell-based transplantation therapy using both iPS and human embryonic stem cells. Those barriers include:

* The ability to make the cell type of interest.

* Safety concerns such as cancer, immune rejection, and preventing a recurrence of the process that originally killed the cells.

* Integration into the body in a physiologically useful form.


While both the cardiovascular and central nervous systems are complex, Thomson believes that cell transplantation will be easier with the heart than with the central nervous system. He noted that scientists already can make heart cells from embryonic stem cells and iPS cells, and they already are screening these cells against potential drugs in ways that won't make the New York Times, but will help people with heart disease.

In contrast, the central nervous system is so complex that cell transplantation could take a long time, he said. In the short term, however, the cells could help scientists understand why Parkinson's disease, for example, occurs in first place. The cells also could lead to therapies to prevent the disease or arrest its progression so people can live productive lives, Thomson said.

Actual transplantation will be very challenging. “It's one thing to make tissue in a culture,” Thomson said. “It's another to get it into the body and re-establish function.”

Tough neighborhood

One scientist who is trying to tackle a nervous system challenge is Lawrence Goldstein, a professor of cellular and molecular medicine at the University of California-San Diego. Goldstein told the summit gathering that cells, including nerve cells, have an “interstate highway system” within them to move biological materials to the right place.

How materials are moved inside cells has led science to some new ideas about conditions like Alzheimer's and Huntington's Disease, and Goldstein said researchers almost have worn out what they can do with animal versions of the diseases using fruit flies and mice. The end of that road has led them to use human pluripotent stem cells, embryonic and induced, to understand how diseases work and how they might be better treated.

One project in Goldstein's lab involves amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, which weakens the muscles by starving them of their nourishment. With this disease, cells called motoneurons, which control the ability of muscle to contract so that people can walk and swallow, die for reasons that are not completely understood. If cell replacement therapy is ever going to treat it, the obvious step is to replace motoneurons that are dying, he said.

“In practice, it is devilishly difficult to do that because some of these motoneuron cells have sizes that are a yard or more along the spinal cord,” Goldstein explained, “and run connections to fingers and toes and to our chest so we can breathe. How to rewire that is a difficult problem to contemplate.”

What his lab has learned in one mouse version of Lou Gehrig's disease is that even though motoneurons are dying, cells immediately surrounding them in the spinal cord can either poison the motoneurons or, if the are normal, rescue them from dying.

“Cells live in neighborhoods, and the quality of the neighborhood has a big impact on the health and viability and education of motoneurons that live in that neighborhood," Goldstein said. “We're trying to use human embryonic stem cells to make cells of the neighborhood and begin implanting them in rat models of Lou Gehrig's disease to see if we can rescue the dying motoneurons.”