June 8, 2012

Connie K. Ho for redOrbit.com

For the first time, scientists at Gladstone Institute have changed skin cells, imbued with a single genetic factor, into cells that can become a group of interconnecting, functional brain cells. The findings show that there may be options in combating neurological conditions. This transformation of cells would pave the way for better methods in testing drugs for neurodegenerative conditions like Alzheimers disease.

The research follows increased interest in Alzheimers disease. Currently, the disorder affects 4.5 million people in the U.S. and, by 2050, the number will have tripled. There are no medications to prevent or reverse Alzheimers Disease at this time.

The findings are published online at Cell Stem Cell and describe how the team of researchers transfer a single cell, known as Sox2, into mouse and human skin cells. Shortly, the skin cells became early-stage brain stem cells called induced neural stem cells (INSCs). The INSCs were able to self-renew and transmit electrical signals. The neurons were able to become neural networks within a month.

Many drug candidates especially those developed for neurodegenerative diseases fail in clinical trials because current models dont accurately predict the drugs effects on the human brain, commented Gladstone Investigation Dr. Yadong Huang, who is also an associate professor of neurology at the University of California, San Francisco (UCSF), in a prepared statement. Human neuronsderived from reengineered skin cellscould help assess the efficacy and safety of these drugs, thereby reducing risks and resources associated with human trials.

Huangs study was based off work done by Gladstone Investigator Dr. Shinya Yamanaka. Yanaka had four genetic factors become adult human skin cells then into embryonic stem cells, otherwise known as induced pluripotent stem cells (iPS cells). The cells can become almost any type of cell in the body. As well, last year, Gladstone Senior Investigator Dr. Sheng Ding found a combination of small molecules and genetic factors that could change skin cells into neural stem cells. These days, Huang uses one genetic factor, Sox2, to directly reprogram cell types without having to resort back to a pluripotent state.

We wanted to see whether these newly generated neurons could result in tumor growth after transplanting them into mouse brains, explained Karen Ring, UCSF Biomedical Sciences graduate student and the papers lead author, in the statement. Instead we saw the reprogrammed cells integrate into the mouses brainand not a single tumor developed.

The findings of the project have shown that Sox2 acts as a master regulator that maintains the identity of neural stem cells. In the future, Huang and his fellow researchers hope that they can identify similar regulators that can help the development of particular neural progenitors and subtypes of neurons in the brain.

If we can pinpoint which genes control the development of each neuron type, we can generate them in the petri dish from a single sample of human skin cells, noted Huang. We could then test drugs that affect different neuron typessuch as those involved in Parkinsons diseasehelping us to put drug development for neurodegenerative diseases on the fast track.

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Scientists Reprogram Skin Cells To Brain Cells