Bioengineer enhances adult stem cell utility

BERKELEY - Adult stem cells carry neither the controversy nor the cachet of embryonic stem cells, but research on the older cells is often clouded by the conflict over their younger cousins.

Now, a UC Berkeley bioengineer has devised a way to enhance the utility of adult stem cells that could steal some of the spotlight away from embryonic stem cells and eventually lead to treatments or cures for diseases such as Alzheimer's and Parkinson's.

David Schaffer and a team of scientists from UC Berkeley and the Salk Institute in San Diego discovered that a certain protein can trigger adult stem cells in the brain to multiply at three times the normal rate.

"We've learned how to make them divide faster," said Schaffer. "And then the brain knows what to do with them, and about half are turned into neurons."

Schaffer used a protein called Sonic hedgehog that is involved with development of the central nervous system in embryos. The protein got its name from the popular video game character because mutating the protein causes fruit fly embryos to grow a small pointy ridge like a hedgehog.

When Sonic hedgehog meets stem cells from rat brains in a petri dish, the stem cells speed up their division. Schaffer's team also found that injecting the gene that creates Sonic hedgehog directly into the brains of live rats pumps up stem cell proliferation.

"If you could do the same thing in a human being, it might enhance the function of the hippocampus which is an area of the brain involved in learning and memory," said Theo Palmer, a neuroscientist at Stanford University.

Though adult stem cells are less versatile than embryonic stem cells, the more mature cells could actually be better suited for certain uses, said Schaffer.

Embryonic stem cells have captured scientists' imaginations because they have the extraordinary ability to grow into many different types of cells. When a stem cell divides, each new cell can either stay a stem cell or develop into a specialized cell, such as a red blood cell or a muscle cell.

Scientists hope to learn how to control which specialized cells the embryonic stem cells become. This would be the first step toward replacing cells damaged by disease or injury.

"The embryonic stem cells are the ultimate blank slate," Schaffer said.

Adult stem cells have already started down the path toward a particular set of specialized cells, such as brain cells. So if it's brain cells that are needed, as in the case of stroke victims or patients with a brain disease, adult stem cells may be easier to work with.

Another advantage of working with adult stem cells is avoiding the ethical firestorm surrounding embryonic stem cells, which can most easily be gotten from human embryos that are a few days old. Because of these concerns, in 2001 the Bush administration decided to limit federal funding for embryonic stem cell research to cell lines that are already in existence.

Though Californian's voted to take up some of the slack by passing Proposition 71, a $3 billion stem cell research initiative that will include embryonic stem cells, research on adult stem cells is also still eligible for federal grants.

Another challenge facing both types of stem cell research down the road will be successful transplantation of the cells into a patient so that they won't be rejected by the immune system.

Schaffer's research could help overcome this hurdle by using a patient's own stem cells, possibly while they are still in the brain.

"It would be easier to have somebody pop a pill that gives the stem cells the signal to make them do what we want them to do," said Schaffer.

Schaffer's team took DNA from a rat and isolated the gene that produces the Sonic hedgehog protein. They then cloned that gene, inserted it into a harmless virus which they then injected into the rat's brain. The virus delivered the Sonic hedgehog genes to the brain stem cells, stimulating them to divide three times faster than normal, which in turn tripled the production of new neurons.

The area of the brain they treated is called the hippocampus, which is involved in learning and memory and is severely affected by Alzheimer's disease. Though it would probably be a decade or more away, Schaffer's research could eventually lead to a treatment or cure for Alzheimer's Disease, and other brain diseases and injuries.

"I think it's very promising," said Ravi Kane, a chemical engineer at Rensselaer Polytechnic Institute in Troy, N.Y. "But at the same time, we're not talking about a cure for Alzheimer's disease in the next two years. It's an exciting avenue, but it's still down the road."

The next step for Schaffer's team is to try to learn how to control the development of stem cells into neurons. They'd also like to be able to generate other types of neurons that would help people with Parkinson's disease and Lou Gehrig's disease.

Schaffer's discoveries also have the potential to help people with depression and people with cancer who are treated with radiation therapy, says Palmer. Recent studies in Palmer's lab and elsewhere suggest that in both of these cases, brain stem cell growth is stunted.