Nobel winner Shinya Yamanaka's stem cell research to be used for retina damage trial

Kyoto University Professor Shinya Yamanaka receives a call Kyoto University Professor Shinya Yamanaka receives a call from Japanese Prime Minister Toshihiko Noda to congratulate him for winning the Nobel Prize in Medicine along with British researcher John B. Gurdon. (Oct. 8, 2012) Photo Credit: AP

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Stem cells derived from a mouse's skin won Shinya Yamanaka the Nobel Prize Monday. Now researchers in Japan are seeking to use his pioneering technology for an even greater prize: restoring sight.

Scientists at the Riken Center for Developmental Biology in Kobe plan to use so-called induced pluripotent stem cells in a trial among patients with macular degeneration, a disease in which the retina becomes damaged, resulting in loss of vision, Yamanaka told reporters in San Francisco Monday.

Companies including Pfizer Inc. are already planning trials of stem cells derived from human embryos. The Japanese study will be the first to use a technology that mimics the power of embryonic cells while avoiding the ethical controversy that accompanies them.

"The work in that area looks very encouraging," John B. Gurdon, 79, a professor at the University of Cambridge who shared the Nobel with Yamanaka Monday, said in an interview in London.

Yamanaka and Gurdon shared the 8 million Swedish kronor ($1.2 million) award for experiments 50 years apart that showed that mature cells retain in latent form all the DNA they had as immature stem cells, and that they can be returned to that potent state, offering the potential for a new generation of therapies against hard-to-treat diseases such as macular degeneration.

Mouse Skin Cell In a study published in 1962, Gurdon took a cell from a tadpole's gut, extracted the nucleus, and inserted it into the egg cell of an adult frog whose own nucleus had been removed. That reprogrammed egg cell developed into a tadpole with the genetic characteristics of the original tadpole, and subsequent trials yielded adult frogs.

Yamanaka, 50, a professor at Kyoto University, built on Gurdon's work by adding four genes to a mouse skin cell, returning it to its immature state as a stem cell with the potential to become any cell in the body. He dubbed them induced pluripotent stem cells.

"There are few moments in science that are undisputed as genuine elegant creativity and simplicity," Alan Trounson, the president of the California Institute for Regenerative Medicine in San Francisco, said in an e-mail. "Shinya Yamanaka is responsible for one of those. An extraordinary accomplishment by a genuinely modest and brilliant scientist." Treatment Variety The technology may lead to new treatments against diseases such as Parkinson's by providing replacement cells.

"The implications for regenerative medicine are obvious," R. Sanders Williams, president of the Gladstone Institutes in San Francisco, where Yamanaka is a senior investigator, said in a telephone interview. "Skin cells can be converted to any other cell you want -- skin to brain or skin to heart, skin to insulin-producing." While Gurdon and Yamanaka's achievements were groundbreaking, treatments based on induced pluripotent cells may be "way down the line," Juleen Zierath, the deputy chairwoman of the Nobel committee that awarded the prize, told reporters in Stockholm Monday.

Scientists first must ensure that the cells are safe, Yamanaka said in a video appearance from Japan Monday at the San Francisco news conference organized by Gladstone. One concern is that stem cells could grow out of control, leading to cancers.

Cell Safety "We need to double check we don't see any severe side effects in patients after transfer," he said. "That's where we have been spending most of our time.

We are getting closer and closer. In some diseases, like macular degeneration, it's almost ready to go." Researchers led by Masayo Takahashi at the Riken center plan to use Yamanaka's technique with the skin cells from patients, turning them into stem cells before cultivating them to become a certain type of retinal cell. Those cells will then be transplanted into the patients' eyes, the Stem Cell News website reported in June, citing Takahashi.

Takahashi and colleagues have already succeeded in transplanting retinal cells into mice. None of the animals developed cancer, the report said.

Ethical Controversy Yamanaka's work sidestepped the ethical controversy surrounding human embryonic stem cell research, in which the cells are extracted from an embryo, which is destroyed in the process. Pfizer, based in New York, plans to start a trial of an embryonic stem cell therapy among patients with macular degeneration next year, according to information on the U.S. National Institutes of Health's clinicaltrials.gov website.

Geron Corp., the Menlo Park, California-based company that started the first U.S.-approved trial of embryonic stem cells, said in November it was abandoning the program because of the costs involved.

Advanced Cell Technology Inc., based in Marlborough, Massachusetts, is also testing a treatment based on embryonic stem cells in patients with macular degeneration. The company uses a technique that doesn't destroy the embryo. Other companies such as Melbourne-based Mesoblast Ltd. are testing adult stem cells derived from bone marrow in heart disease.

Apart from the ethical advantage, induced pluripotent stem cells are less likely to be rejected by a patient's immune system because the cells are their own, said Konrad Hochedlinger, a researcher in the department of stem cell and regenerative biology at Harvard University.

"This method allows us to create patient-specific cells," Hochedlinger said in a telephone interview.

Other applications may be to study diseases such as Alzheimer's, or to test drugs against certain types of cells in a lab dish without the risks of side effects, Gurdon said.

"If you can take cells from a patient, like a patient with a neurodegenerative disease, and grow those in culture in the laboratory, you can test drugs on them easily," Gurdon said. "To be able to derive cells that reflect a disease, in culture, is immensely important."

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