New method makes stem cell function of liver cells
British scientists have developed a technique of stem cells to grow new liver cells that could work to avoid the need for liver transplants costly and risky.
A team of researchers led by the Sanger Institute and the University of Cambridge using cutting-edge methods to correct a genetic mutation in stem cells derived from skin biopsy of a patient and then grown in fresh liver cells.
By putting the new liver cells in mice, demonstrated that they were in full operation.
"We have developed new systems of target genes and ... right ... defects in patient cells," said Allan Bradley, director of the Sanger Institute.
At a briefing on the work, Bradley said the technique - the first success of this type - leaves no trace of genetic manipulation, except for gene correction.
"These are the first steps, but if this technology can have on treatment, which will offer great benefits for patients," he added.
Stem cells are master cells of the body, the source of all other cells. Scientists say it could transform medicine, offering treatments for blindness, spinal cord and other injuries, and new cells of damaged organs.
The research focuses on two major embryonic stem cell shapes, which are extracted from embryos and the reprogrammed cells, also known as induced pluripotent stem cells or iPS cells that are reprogrammed skin or normal blood cells.
When they were first discovered in 2006, iPS cells appeared to be a perfect solution to the ethical debate about using embryonic stem cells because they are made in a laboratory of the skin or normal blood cells. Embryonic stem cells are harvested from surplus embryos at fertility clinics and their use is opposed by many religious groups.
But in recent years there have been concerns that iPS cells may not be as "clean" or as capable as embryonic cells.
Last year, a group led by Robert Lanza, technology U.S. company Advanced Cell, compared to lots of iPS cells with embryonic stem cells and iPS cells died more quickly noticed and were much less able to grow and expand.
The correction of the mutation
In the study on Wednesday in the journal Nature, the British team took skin cells from a patient with a mutation in a gene called alpha-1-antitrypsin, which is responsible for a protein that protects against inflammation.
People with mutant alpha 1-antitrypsin are unable to release adequate protein from the liver, so it gets trapped there and eventually leads to liver cirrhosis and pulmonary emphysema. This is one of the most common inherited liver and lung disorders, affecting about one in 2,000 people of northern European origin, the researchers said.
Having reaped the skin cells, the scientists reprogrammed back into stem cells and then used a type of "molecular scissors" technique known as a zinc finger nuclease to cut the genome of the cells at precisely the place and insert the correct version of the gene using a DNA transporter called piggyBac.
The sequences of the piggyBac remains were removed from the cells, cleaning them and allowing them to become liver cells, with no trace of residual DNA damage at the site of gene correction.
"Then he turned those cells in human liver cells and put into a mouse and showed that they were viable," said David Lomas, a Cambridge professor of biology in the airways who also worked on the team, the journalists at the press conference.
Ludovic Vallier, also of Cambridge University, said the results were a first step toward personalized cell therapy for genetic liver disorder. "We still have significant challenges to overcome ... but we now have the tools," he said.
The researchers said it could be five to 10 years before full clinical trials of the technique could work with patients with liver disease. But if they succeed, the liver transplant procedure, costly and complicated, where patients need a lifetime of drugs to ensure that the new organ is not rejected, it could become a thing of the past.
"If we use the patient's own cells to produce skins of liver cells that can be put back into the patient, you can avoid the future need for transplant," said Lomas.
New method makes stem cell function of liver cells
