Breakthrough as stem cells are produced from skin, not embryos - Times Online

http://www.timesonline.co.uk/tol/life_and_style/health/article2908408.ece

Mark Henderson, Science Editor

Scientists say they have succeeded in genetically reprogramming skin tissue to create powerful “master” cells that are as versatile as the stem cells from human embryos — and which can help in the development of treatments for diseases such as Parkinson’s and diabetes.

The reprogrammed cells have the potential to form any kind of human tissue, according to two separate research teams, from Japan and the United States.

The results allow for a new approach to stem-cell therapy that skirts some of the ethical and practical problems that have limited its progress to date, such as the destruction of human embryos. Once perfected, the technique would allow scientists to take skin cells from patients with conditions such as diabetes and spinal paralysis, and turn them into stem cells. These could then be grown into “spare part” tissue, which could be transplanted without fear of rejection by the body’s immune system because the cells are genetically the patient’s own.

The method requires neither cloning nor the destruction of human embryos, regarded as immoral by many religious groups. It also gets round the shortage of human eggs and surplus embryos, which has held up research into stem cells and therapeutic cloning.

Both teams of scientists said, however, that the advance in no way implied that embryonic stem cell research was outdated or unethical, and they insisted that the older method must proceed in parallel to the new approach to give the best chance of progress. The reprogramming technique could not have been developed without extensive study of embryonic stem cells, and the so-called induced pluripotent stem cells it produces are slightly different from the real thing.

Professor Jamie Thomson, of the University of Wisconsin-Madison, who led one of the studies, said: “It is hardly time to discontinue embryonic stem cell research.”

The new type of stem cells were also made by manipulating genes with a virus that might induce mutations that could cause cancer and one of the altered genes is known to be implicated in some tumours. That means that more research will be needed before the cells can be used for therapy, but they could have immediate applications for investigating genetic disease.

Cells could be taken from patients with conditions such as Parkinson’s or motor neuron disease, then reprogrammed and grown into nerve cells for studying the progress of the disorders and testing new drugs.

Embryonic stem cells have excited scientists since they were first derived from human embryos by Professor Thomson in 1998, because they have the potential to form any tissue in the human body. They could thus be used to treat diseases in which cells become damaged or die, and if produced from cloned embryos they could be precisely matched to individuals.

The field has been hampered by a shortage of eggs and embryos for research, and by ethical objections to the destruction of embryos that led the Bush Administration to ban most embryonic stem-cell work in the United States. It is permitted under licence in Britain.

The new technique could overcome both issues. It was developed by Shinya Yamanaka, of the University of Kyoto, who first performed it in mice last year. It involves replacing four genes known as Oct3/4, Sox2, Klf4 and c-Myc in skin cells known as fibroblasts using a viral vector.

Dr Yamanaka’s team has now repeated the feat with human fibroblasts, taken from the facial skin of a woman aged 36 and the connective tissue of a man aged 69. His results, published in the journal Cell, show that ten lines of the new type of stem cells were produced from 50,000 skin cells, a success rate of one in 5,000.

Professor Thomson has achieved much the same thing by manipulating a slightly different set of genes. His results, published in Science, are slightly less impressive as the success rate was only one in 10,000, and the cells came from foetal skin and the foreskin of a newborn boy rather than from adults.

Dr Yamanaka said: “We should now be able to generate patient and disease-specific iPS cells, and then make various cells, such as cardiac cells, liver cells and neural cells. These cells should be extremely useful in understanding disease mechanisms and screening effective and safe drugs. If we can overcome safety issues, we may be able to use human iPS cells in cell transplantation therapies.”

Professor Thomson said: “The induced cells do all the things embryonic stem cells do. It is going to completely change the field. Immune rejection should not be a problem using these cells.”

Both scientists said that embryonic stem-cell research must continue, to ensure that the induced cells behave in the same way as their embryonic counterparts.

Independent stem cell experts hailed the studies as highly important. Professor Azim Surani, of the University of Cambridge, said: “It is relatively easy to grow an entire plant from a small cutting, something that seems inconceivable in humans. Yet this study brings us tantalisingly close to using skin cells to grow many different types of human tissues.”

Professor Robin Lovell-Badge, of the National Institute for Medical Research, said: “This approach is going to open up research into the genetic causes of disease and the search for therapies not only for such diseases, but also for repairing tissues damaged in other ways.”