Study of iPS cells draws nearer to finding cures

Research in stem cells and the origin and treatment of disease is definitely moving away from destructive embryonic stem cell research toward induced pluripotent stem cells (iPS).

A fantastic review that connects Japan's Dr. Yamanaka, San Francisco's Srivastava, the University of Texas Southwestern Medical Center in Dallas, and the Burnetts of Sulphur Springs, Texas, is published in the Japan Times. (Written by Rob Waters for Bloomberg news.)

Yamanaka, a professor at Kyoto University, developed a technology that may make the argument moot. Yamanaka, who has two daughters, started his effort 10 years ago, after peering at a tiny embryo through a microscope and reflecting that it might form a child if it wasn't used to make stem cells, he said in an interview.

"That's the moment I thought about this project," he said. "I saw that if we could make pluripotent stem cells without using human embryos, that would be ideal."

In 2006, he scored his first success. Using a virus to insert four genes into the skin cells of mice, he started a process that returned the cells to a primordial state able to form any other cell in the body. Yamanaka named them induced pluripotent stem, or iPS, cells. The next year, he repeated the feat with human cells.

Yamanaka and researchers elsewhere are now racing to find better ways to achieve the same effect. They would like to get rid of the virus, which can cause the genes to lodge permanently in the structure of the cell and may trigger the growth of tumors.

Yamanaka's technique exploits a basic fact of human biology — that every cell in a person contains the genetic instructions that set that person's traits, from hair color to inherited disease. By taking skin cells from a person with a disease and turning them into cells in the heart, brain or pancreas that are affected by a genetic disease, researchers can experiment with disorders at their earliest stages, Harvard's Melton said.

Labs are now creating iPS cells because making them is far simpler than getting cells from embryos, said Jeanne Loring, founding director of the Center for Regenerative Medicine, part of the Scripps Research Institute in La Jolla, Calif.

"Every stem-cell researcher I know has made about a dozen," Loring said.

She estimates that researchers have made 300 different so-called lines of iPS cells, a number that may double this year. Each line is a colony of cells descended from the first ones made. Scientists keep them alive in culture and the cells keep replicating.

Grants of $23 million awarded last June by the California Institute for Regenerative Medicine, the state's stem-cell funding agency, show that researchers are embracing iPS cells. Of 16 grants awarded, eight went to teams developing new iPS cells and five to groups comparing iPS and embryonic cell types. Just three went to scientists proposing to work solely with embryonic cells, according to the San Francisco-based agency.(Emphasis mine.)

And actual treatments are coming soon:

In 2004, Srivastava, then working at the University of Texas Southwestern Medical Center in Dallas, went with colleagues to Sulphur Springs, Texas, to collect blood samples and perform ultrasound scans on members of the Burnett family.

The researchers analyzed the genes of family members and found that 11 had heart-valve defects linked to mutations in a gene called Notch1, which plays a role in the formation of many organs, including the heart.

People with this mutation make half as much of the Notch1 protein as they should and their heart valves develop abnormally. The protein shortage primes their valves to take on extra calcium, which, over time, makes them stiffen, malfunction and require replacement.

Four years after his Notch1 discovery, Srivastava, now the director of the J. David Gladstone Institute of Cardiovascular Disease, supervised as the Burnetts had a pencil-shaped skin punch pushed into their calves to extract a bit of skin. When the boy's turn came, his 12-year-old brother, Ryan, laid a comforting hand on his back.

The iPS cells made from the Burnett's skin will be coaxed to become heart cells that carry the Notch1 mutation, Srivastava said. He plans to use the cells to test for drugs that boost levels of the Notch1 protein. This, he reasons, should make the hearts of people like the Burnetts more resistant to the entry of calcium and reduce the mineral's buildup on the valves.

A drug that could do this may essentially prevent the disease, Srivastava said. That is because the condition is present at birth, yet symptoms usually take decades to develop, giving a medicine ample time to work.

Within five years, Srivastava predicts, he will have found the right drug and be ready to start human clinical tests. A closely held company named iZumi Bio Inc., in California, will collaborate with Srivastava on this and other research involving iPS cells, Seidenberg of Kleiner Perkins said.