Science

Scientists fix gene mutation in stem cells, then grow hepatocytes

Last Updated: 2011-10-12 18:35:21 -0400 (Reuters Health)

By Kate Kelland

LONDON (Reuters) - British scientists have developed a new stem cell technique for growing hepatocytes that could eventually avoid the need for costly and risky liver transplants.

A team of researchers led by the Sanger Institute and the University of Cambridge corrected a mutation in the alpha1-antitrypsin gene in stem cells derived from a patient's skin biopsy, and then grew them into fresh liver cells that were fully functional in mice.

At a briefing about the work, Allan Bradley, director of the Sanger Institute said the technique -- the first success of its kind -- leaves behind no trace of the genetic manipulation, except for the gene correction.

"These are early steps, but if this technology can be taken into treatment, it will offer great possible benefits for patients," he added.

As the researchers noted in their report online today in Nature, people with the alpha1-antitrypsin mutation develop liver cirrhosis and lung emphysema. This is one of the most common inherited liver and lung disorders and affects about one in 2,000 people of North European origin, the researchers said.

Having harvested the skin cells, the scientists reprogrammed them back into stem cells and then used a type of "molecular scissor" technique known as a zinc finger nuclease to snip the cells' genome at precisely the right place and insert a correct version of the gene using a DNA transporter called piggyBac.

The leftover piggyBac sequences were then removed from the cells, cleaning them up and allowing them to be converted into liver cells without any trace of residual DNA damage at the site of the genetic correction.

"We then turned those cells into human liver cells and put them in a mouse and showed that they were viable," David Lomas, a Cambridge professor of respiratory biology who also worked on the team, told reporters at the briefing.

Ludovic Vallier, also from Cambridge University, said the results were a first step toward personalized cell therapy for genetic liver disorders. "We still have major challenges to overcome...but we now have the tools necessary," he said.

In their paper, the researchers wrote, "This approach is significantly more efficient than any other gene-targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle, to our knowledge, for the potential of combining human induced pluripotent stem cells with genetic correction to generate clinically relevant cells for autologous cell-based therapies."

The researchers said it could be another five to 10 years before full clinical trials of the technique could be run using patients with liver disease. But if they succeed, liver transplants could become a thing of the past.

"If we can use a patient's own skins cells to produce liver cells that we can put back into the patient, we may prevent the future need for transplantation," said Lomas.

SOURCE: http://bit.ly/nITai8

Nature 2011.