Scientists create molecule that causes nerve stem cells to mature

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London, June 16 : Researchers at UT Southwestern Medical Center claim to have made a small molecule that stimulates nerve stem cells to begin maturing into nerve cells in culture.

The researchers hope that someday their work might open the door for a potential new technology to grow a person's own nerve stem cells outside the body, stimulate them into maturity, and then re-implant them as working nerve cells to treat various diseases.

"This provides a critical starting point for neuro-regenerative medicine and brain cancer chemotherapy," Nature magazine quoted Dr. Jenny Hsieh, assistant professor of molecular biology, as saying.

She said that creation of the molecule helped her team uncover some of the biochemical steps that happen as nerve cells mature, and showed that large-scale screening of compounds could provide starting points for developing drugs to treat disorders like Huntington's disease, traumatic brain injury or cancer.

She revealed that the research group started work on this project as a result of a separate study wherein 147,000 compounds were being screened to see which of them could stimulate stem cells cultivated from rodent embryos to become heart cells.

Dr. Hsieh said that five molecules were found to stimulate the cells to transform into forms resembling nerve cells.

She added that the team then created a variation of those molecules, a new compound called Isx-9 (for isoxazole-9).

According to her, it was easier to use Isx-9 than its initially discovered relatives, as it worked at a much lower concentration and dissolved more easily in water.

"It was completely serendipitous that we uncovered this neurogenic [nerve-creating] small molecule. I think it's one of the most powerful neurogenic small molecules on the planet. In theory, this molecule could provoke full maturation, to the point that the new nerve cells could fire, generating the electrical signals needed for full functioning," she said.

Dr. Hsieh revealed that she and her colleagues cultured rodent nerve cells from an area of the brain called the Hippocampus with Isx-9.

She said that the cells clustered together, and developed spiky appendages called neuritis, which typically happens when nerve cells are grown in culture.

The study also showed that Isx-9 prevented the stem cells from developing into non-nerve cells, and that it was more potent than other neurogenic substances in stimulating nerve-cell development.

The molecule generated two to three times more nerve cells than other commonly used compounds, said Dr. Hsieh.

She further said that Isx-9 appeared to act like a neurotransmitter-like signal which, when sent by a mature nerve cells, enabled the immature cells to begin maturing.

When the researchers cultured the stem cells with the compound, said Dr. Hsieh, they identified a possible biochemical pathway whereby stem cells begin to become nerve cells.

Dr. Hsieh and her colleagues are now planning to test Isx-9 on a large number of different combinations of RNA, the chemical cousin of DNA, to see on which genes the compound might be working.

The research team has also applied for a patent on Isx-9 and its relatives.

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