Canadian researchers have discovered a new way to turn skin cells into stem cells with fewer potential risks to patients.
Their work removes major barriers to using stem cells, which have an endless capacity for self-renewal, in new medical therapies for people with spinal cord injuries or diseases such as diabetes or Parkinson's.
"We hope these stem cells will form the basis for treatment of many diseases and conditions that are currently considered incurable," says Andras Nagy, of Toronto's Mount Sinai Hospital. He is the lead author of a groundbreaking paper published online Sunday by the journal Nature.
Dr. Nagy and his colleagues are the first to reprogram human skin cells to an embryonic state without using a virus, collaborating on the new technique with Keisuke Kaji from the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh.
Dr. Nagy's team has been working full-out for a year on this novel approach, which builds on a breakthrough reported by Japanese and American researchers in November, 2007.
The Japanese took skin cells from the face of a 36-year-old woman and turned them into cells that look and act like embryonic stem cells. The Americans did the same with skin cells from infant foreskins.
In the developing embryo, stem cells give rise to every type of cell in the body: skin, muscle, bone, heart, liver, kidney, brain and 250 other types of specialized cells. The 2007 advance made headlines because it allowed scientists to sidestep the ethical debate over getting stem cells for medical research from aborted fetuses.
But there were two major problems with the technique.
Both the Japanese and American teams used viruses to insert four genes that are active in stem cells into the genome of the mature skin cells.
Viruses can damage healthy DNA. Some of the genes that orchestrated the transformation back to an embryonic state can also cause cancer.
Dr. Nagy and his colleagues have developed a technique to make stem cells without either of these drawbacks.
Without using a virus, they were able to slip four genes into skin cells that reprogrammed them to an embryonic-like state. They were also able to then get rid of the genes with the potential to cause cancer.
How did they do it? The team used a jumping gene, a mobile piece of DNA also known as a transposon. In moths, corn and other species, these genes hop from chromosome to chromosome, inserting themselves randomly into the genome. They give rise to the kind of genetic variability that can help species adapt to changing conditions.
First, Dr. Nagy and his colleagues inserted the four reprogramming genes into a jumping gene from a moth. Then they put the jumping gene and its cargo into a skin cell.
The jumping gene cut and pasted the stem cell genes into a chromosome in the skin cell. The scientists were then able to coax the skin cell back to its embryonic state, giving it the superhero-like ability to turn into many types of cells.
In many cases, they found that the jumping gene then took a second leap to another chromosome. But 60 per cent of the time, the second cut-and-paste operation wasn't successful. This meant the four genes were not reinserted back into the genome of the skin cell, and disappeared, as did the jumping gene.
"It goes back to the original," Dr. Nagy said.
The Canadian researchers were able to easily identify the stem cells that were no longer carrying the four genes.
The work is a "great advance," says the University of Ottawa's Michael Rudnicki, a leading stem cell researcher who is not involved in the study.
"These will be relatively pristine cells that can certainly be exploited therapeutically and will be useful for research purposes," he said.
Many scientists believe that the flexibility and regenerative power of stem cells hold great promise in the treatment of many diseases, including Alzheimer's, and that one day they may be used to repair damaged hearts, kidneys, livers or other tissue, or even to grow new organs for transplant.
Dr. Nagy's team performed the experiments on both mouse and human cells. They are now using their technique to grow stem cells from the mature cells taken from patients suffering from a variety of diseases, including cystic fibrosis.
One day, the work could allow patients to be treated with their own reprogrammed stem cells. But Dr. Nagy said it is difficult to predict how soon that could happen.