'Flipping the switch:' Skin cells provide benefits of stem cells

By Lou Fancher Correspondent San Jose Mercury News

LAFAYETTE -- In the land inhabited by Dr. Deepak Srivastava, miracles begin in petri dishes.

One of those miracles resulted in an Oct. 8 announcement: Dr. Shinya Yamanaka, a researcher Srivastava originally hired in 1993 to study fat metabolism, had won the 2012 Nobel Prize in Medicine, sharing the honor with Dr. John Gurdon of the University Of Cambridge.

At a late October Lafayette Library and Learning Center Foundation Science Café session, Srivastava -- senior investigator at the Gladstone Institute of Cardiovascular Disease in San Francisco -- explained the science behind Yamanaka's groundbreaking discovery, and how it might change how medicine looks in 10 years.

Building on Gurdon's own discovery that a modified egg cell can convert itself, Yamanaka found a way to take an adult skin cell and, by introducing four master genes, flip the switch to create what is now called an "induced pluripotent stem cell." These IPS cells, made from one's own body, outmaneuver the immune system's tendency toward rejection. Within three weeks of switch-flipping, IPS cells behave like embryonic cells and can be implanted.

"This is like science fiction; we never thought we'd be able to do this," Srivastava said as he brought up a video of thousands of skin cells, beating like a human heart in complete synchronicity.

Gladstone researchers have changed fibroblast cells (the most common cells of connective tissue in animals) into brain, blood and liver cells. In the future, Srivastava expects conversion of insulating cells surrounding the spinal cord and non-insulin-producing cells to help the patients he used to see as a practicing pediatrician.

"Imagine 'personalized medicine,' where clinical trials in a dish -- instead of the toxicity of doing it in your body -- can lead to the discovery of new drugs," he suggested.

"What if we could take your skin cells and make new cells for your damaged heart? What if we could segregate the individuals who would have a bad side affect from a drug by testing their cells, not those of a mouse? What if we redeployed nature's own tool kit to make new heart cells?"

Srivastava described current post-heart attack cardiovascular treatment -- a rush to the hospital and delivery of medicine the doctor knows will help only seven out of 10 patients, and that will end the life of the one out of 10 who suffers an adverse reaction to it.

In cases where the heart is so damaged it must be replaced, a patient logjam is equally treacherous.

"We do 2,000 heart transplants in this country each year, but that's not enough because there are 5 million people with heart disease," he says.

Alzheimer's, diabetes, dementia, Parkinson's, ALS, HIV and immune diseases like hepatitis C -- all diseases in need of a cure are looking to stem cell biology to create new ideas and make revolutionary, game-changing discoveries, Srivastava claimed.

But embryonic cells, until recently, have been the only stem cells capable of regenerating, of converting themselves into heart, liver and other cell forms. Cultivating them results in destruction of the five-day-old embryos in which they are found -- a practice whose ethical implications are a tripwire in both the U.S. and in Yamanaka's native country, Japan.

"One of the reasons I was able to recruit him is that it was terrifically difficult, if not impossible, for him to do this kind of research in Japan," Srivastava said in an interview before his presentation. "Until recently, they didn't even allow transplants."

Audience questions brought up the costs and relevant ethical questions relating to stem cell research.

Srivastava said tailored medicine is likely to target and decrease the cost of medical treatment. Continued embryonic stem cell research is a must, because understanding how to make them stop dividing is providing scientists with clues into arresting the prolific growth of cancer cells, nature's counterpart to embryonic cells.

"They are the gold standard. But with IPS cells, we get around a lot of the ethical issues. The issue is not gone -- we may get the question, 'Are you playing God?' -- but for now, we've got a technology that will allow everyone to get on board."