Skins cells turned into brain cells in stem cell breakthrough

Scientists used just three genes to make the identity switch, which was achieved without an in-between stem cell stage.

The breakthrough could “revolutionise the future of human stem cell therapy” for the regeneration of brains, said the researchers.

In the past, normal cells have been coaxed into changing function by first turning them into “induced” stem cells.

These have similar properties to stem cells taken from embryos, giving them the potential to become any kind of tissue in the body.

The new research went a step further by transforming mouse skin cells straight into functional neurons, while by-passing the stem cell process.

Dr Marius Wernig, who co-led the team from Stanford University School of Medicine in California, said: “We actively and directly induced one cell type to become a completely different cell type.

“These are fully functional neurons. They can do all the principal things that neurons in the brain do.”

In the laboratory dish, the cells were seen to signal and make connections with other nerve cells. Such functions are critical to future treatments for Parkinson’s disease and other brain disorders.

The change happened within one week with an efficiency of almost 20 per cent.

The scientists, whose research is published in the journal Nature, now hope to duplicate the feat with human cells.

Dr Irving Weissman, director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, said: “This study is a huge leap forward. The direct reprogramming of these adult skin cells into brain cells that can show complex, appropriate behaviours like generating electrical currents and forming synapses establishes a new method to study normal and disordered brain cell function.

“Finally we may be able to capture and study conditions like Parkinson’s or Alzheimer’s or heritable mental diseases in the laboratory dish for the first time.”

In 2007, researchers announced the creation of iPS cells from human skin cells by exposing them to proteins called transcription factors that influence DNA.

Once in a stem cell-state, a cocktail of chemicals was used to make the cells develop into a new cell type.

Later, scientists from Harvard University in the US showed that mouse pancreas cells could be reprogrammed by infecting them with viruses carrying genes for just three transcription factors.

Dr Wernig’s team used a similar technique, but dispensed with the iPS “pit stop”.

The scientists began with a selection of 19 genes involved in either genetic reprogramming or neural development and function.

A virus was used to introduce the genes to mouse embryo skin cells, which were then monitored.

After 32 days, some of the former skin cells had acquired the appearance of nerve cells and were producing neural proteins.

The process was used to whittle the original 19 genes down to just three, which were then tested on skin cells from the tails of adult mice.

About 20 per cent of the former skin cells transformed themselves into neural cells in less than a week. In comparison, it can take weeks to change a cell’s identity using the iPS method, with a success rate of just 1% to 2%.

“We were very surprised by both the timing and the efficiency,” said Dr Wernig. “This is much more straightforward than going through iPS cells, and it’s likely to be a very viable alternative.”

The ability to make neurons quickly from an individual patient may one day lead to the manufacture of cells for therapy, the scientists believe.

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