Chemist Cites Advance in Stem-Cell Field 23

By GAUTAM NAIK

Scientists have reprogrammed mature skin cells into an embryonic-like state by using proteins instead of genes, a key advance aimed at overcoming safety concerns in one of the hottest areas of biological research.

The stem-cell field has long aimed to harness the master cells of a human embryo, which can be turned into heart, nerve and other types of tissue. The long-term hope is that such tissue could be used to test novel drugs, or be transplanted into patients to treat diseases. But because the cell extraction destroys the embryo, the technique has ignited much ethical controversy.

In the past few years, scientists have found an alternative approach. By introducing several genes into a mature human cell, they have been able to reprogram it to a primitive, embryonic-like state. The approach carries risks, however. The genes are transported with the help of a virus, which can cause cancer. Plus, the DNA of the inserted genes may trigger other unwanted genetic changes in the target cell.

Now, instead of reprogramming the cell with four introduced genes, researchers have achieved the same result by inserting four proteins associated with those genes. This technique is deemed to be safer because it doesn't require genetic manipulation.

"We engineered these four proteins so that they can penetrate the cell" and return it to a primitive state, said Sheng Ding of Scripps Research Institute in La Jolla, Calif., who led the research, which involved several institutions. The results are published in the online version of the journal Cell Stem Cell.

The science of reprogramming is at an extremely early stage. The latest experiment was done on a type of skin tissue known as fibroblasts, taken from mice. Dr. Ding now hopes to replicate the results with human cells. In addition, reprogramming remains a slow and inefficient approach, and would have to be drastically improved before it can be considered for clinical use.

For now, there is considerable progress toward making the technique safer. One team of scientists reprogrammed mouse cells by using an adenovirus, a less harmful type of transport vehicle. Another managed to remove the inserted viruses and genes once their job was finished. Dr. Ding, a chemist, said the ideal would be to avoid biological material entirely, and reprogram cells using molecules alone.

A race is on to commercialize the technique. Dr. Ding is a founder of Fate Therapeutics and Stemgent Inc., both based in San Diego. The biotech start-ups have teamed up to provide reprogramming-derived tissue to pharmaceutical companies involved in drug discovery. Earlier this month, another start-up, iZumi Bio Inc. of South San Francisco, struck a similar deal with Japan's Kyoto University, where the earliest reprogramming breakthroughs occurred.