Stem Cell Study, In Reverse

[Guest guest]

http://www.latimes.com/news/science/la-sci-yamanaka-20101127,0,3440008.story

Reverting cells to their embryonic state, without the embryos

Dr. Shinya Yamanaka of Japan discovered so-called iPS cells, which pave the way

for pursuing regenerative medicine therapies without destroying embryos

Perhaps no scientist has had a greater impact on stem cell research than Dr.

Shinya Yamanaka. While most of his colleagues were looking for ways to grow

human embryonic stem cells into replacement tissues for treating patients, the

Japanese researcher took the opposite approach and figured out how to rewind

mature body cells to a flexible state in which they could again become many

types of cells. His 2006 discovery of induced pluripotent stem cells, or iPS

cells, paves the way for pursuing regenerative medicine therapies without the

need to destroy embryos.

Yamanaka's primary lab is at Kyoto University in Japan, but he spends part of

the year at UC San Francisco's Gladstone Institute of Cardiovascular Disease,

where he was a postdoctoral fellow in the 1990s. On Nov. 10 he received the

$610,000 Kyoto Prize, which recognizes " significant contributions to the

betterment of humankind, " for his stem cell work. He has also won the Albert

Lasker Basic Medical Research Award, the Shaw Prize and the Koch Prize.

He recently spoke with The Times.

What prompted you to start working on iPS cells?

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In 2000, I became interested in how embryonic stem cells maintain their ability

to develop into different kinds of cells. At the time, many laboratories were

trying to turn embryonic stem cells into various functional cells. I thought the

field was highly competitive, so I decided to go the opposite direction —

[turning body cells] back to the embryonic state.

What advantages do iPS cells have over embryonic stem cells?

IPS cells can circumvent two obstacles faced by embryonic stem cells. One is the

ethical controversy — we have to destroy embryos to isolate embryonic stem

cells. The other is the risk of immune rejection when cells derived from

embryonic stem cells are transplanted into a patient's body.

Do they have any disadvantages?

The safety of the cells. They are made by using retroviruses to introduce genes

into mature cells, but the process can cause iPS cells to grow tumors if the

retrovirus is inserted in the wrong part of the genome.

What is the long-term potential of these cells?

IPS cells can become an effective research tool for modeling drugs, screening

drug compounds and testing for side effect or toxicity. In the future, when the

safety and other issues are solved, iPS cell-derived functional cells may become

sources for cell transplantation therapies.

What surprised you most about your research as it unfolded?

When our group succeeded in generating iPS cells, I never imagined so many

researchers would begin working on this new technology — or that the research

would advance at such a rapid pace.

What are the primary scientific hurdles that remain with iPS cells?

Scientists need to find out the methods to generate safer iPS cells, how to turn

those cells into functional cells, and how to transplant resultant cells into a

body. We also need to figure out how to use the cells to study diseases in the

lab.

In the United States, the first clinical trial involving a therapy derived from

human embryonic stem cells has just gotten underway. How do you feel about the

pace of translating research into actual treatments?

The clinical trial using embryonic stem cells took a long time partly because

use of the cells has caused an ethical controversy around the world. It is also

true that it generally takes many years to turn basic research into clinical

applications.

Some question why human embryonic stem cell research should continue when your

discovery allows scientists to generate similar cells without destroying human

embryos. What do you think?

Embryonic stem cells are still important for the development of iPS cell

research. Findings from research on embryonic stem cells, such as methods to

create various types of cells, have been applied to iPS cell research. That's

why iPS cell research has evolved so rapidly. In addition, embryonic stem cells

are used as control [comparison] materials when researchers conduct experiments

on iPS cells and analyze their quality.

Many people speculate that you will win a Nobel Prize one day. Does that make it

hard to get your work done?

I know some people have high expectations, but my concern is not thinking about

winning a Nobel Prize. I worry about what I should do to bring iPS cell

technology from the laboratory to the bedside as soon as possible.