New stem cell method makes functioning liver cells

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By Kate Kelland

LONDON | Wed Oct 12, 2011 3:57pm EDT

LONDON (Reuters) - British scientists have developed a new stem cell technique for growing working liver cells which 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 used cutting-edge methods to correct a genetic mutation in stem cells derived from a patient's skin biopsy, and then grew them into fresh liver cells.

By putting the new liver cells into mice, they showed they were fully functioning.

"We have developed new systems to target genes and ... correct ... defects in patient cells," said Allan Bradley, director of the Sanger Institute.

At a briefing about the work, Bradley 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.

Stem cells are the body's master cells, the source for all other cells. Scientists say they could transform medicine, providing treatments for blindness, spinal cord and other severe injuries, and new cells for damaged organs.

Research is focused on two main forms -- embryonic stem cells, which are harvested from embryos, and reprogrammed cells, also known as induced pluripotent stem cells or iPS cells, which are reprogrammed from ordinary skin or blood cells.

When they were first discovered in 2006, iPS cells looked like a perfect solution to the ethical debate over the use of embryonic stem cells because they are made in a lab from ordinary skin or blood cells. Embryonic stem cells are usually harvested from leftover embryos at fertility clinics and their use is opposed by many religious groups.

But in recent years, concerns have been raised that iPS cells may not be as "clean" or as capable as embryonic cells.

Last year, a group led by Robert Lanza, of the U.S. firm Advanced Cell Technology, compared batches of iPS cells with embryonic stem cells and noticed the iPS cells died more quickly and were much less able to grow and expand.

CORRECTING MUTATION

In Wednesday's study, published in the journal Nature, the British team took skin cells from a patient with a mutation in a gene called alpha1-antitrypsin, which is responsible for making a protein that protects against inflammation.

People with mutant alpha1-antitrypsin are not able to release the protein properly from the liver, so it becomes trapped there and eventually leads to 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.

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 -- costly and complicated procedures where patients need a lifetime of drugs to ensure the new organ is not rejected -- 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.

(Additional reporting by Simon Roach; Editing by Tim Pearce)

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Human 'cloning' makes stem cells

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5 October 2011 Last updated at 18:04 GMT By James Gallagher Health reporter, BBC News Lead scientist Dr Dieter Egli: "Research gives hope for making cells to cure human disease in the future"

A form of cloning has been used to create personalised embryonic stem cells in humans, say researchers.

Genetic material was taken from an adult skin cell and transferred into a human egg. This was grown to produce an early embryo.

Stem cells have huge potential in medicine as they can transform into any other cell type in the body.

However, the stem cells formed contained chromosomes from both the adult and the egg cells.

The technique used - somatic cell nuclear transfer - shot to fame in 1997 when Dolly the sheep, the first mammal to be cloned from an adult cell, was unveiled to the world.

A South Korean scientist, Hwang Woo-suk, had claimed to have created stem cells from cloned human embryos, but was found to have faked the evidence.

The lead researcher at the New York Stem Cell Foundation Laboratory, Dr Dieter Egli, said there was "a great question mark" about whether the cloning technique could be reliably used in humans.

Dolly the sheep

He said other "groups had tried before, but failed".

Writing in the journal Nature, he said his group had also failed using traditional techniques.

When they removed the genetic material from the egg and replaced it with the chromosomes from a skin cell, the egg divided but failed to go past the 6-12 cell stage.

However, when they left the egg's own genetic material in place and added the skin chromosomes, the egg developed. It reached the blastocyst stage, which can contain up to 100 cells and is the usual source of embryonic stem cells.

Eggs and sperm both have one set of chromosomes, which combined means adults have two copies of each chromosome.

In this technique the two adult copies are added to the single copy in the egg meaning a total of three, which can be problematic.

Continue reading the main story

Many diseases are impossible to treat. As the researchers put it they "cannot be cured, they can only be cared for".

Stem cells are one of the great hopes of medicine because they can turn into any other type of cell - nerve, heart, bone, skin, liver etc.

Create heart cells and it might be possible to repair the damage from a heart attack. Insulin-producing cells are destroyed in patients with type 1 diabetes, but stem cells could one day be used to grow more.

There are already clinical trials taking place. The first embryonic stem cell trial in Europe, testing a treatment for progressive sight loss, has started in London.

However this does not use the patient's own cells. Immunosuppressant drugs are likely to be needed to prevent rejection. This is why making stem cells from the body's own cells is seen as such a gold standard of medicine.

Often embryos without the correct number of chromosomes do not develop at all. Down's syndrome is caused by three copies of just one chromosome.

Researchers will need to produce embryonic cells which have only donor DNA, however, once the egg starts to divide the chromosomes are combined in the nucleus and would be near impossible to separate.

Dr Egli told the BBC: "The cells we have made are not yet for therapeutic use. There is clearly more work to be done, this is early days.

"We see this as a step on that road, so now we do know that a human egg can turn an adult specialised cell, such as a skin cell, into a stem cell."

Prof Mary Herbert, from the Institute for Ageing and Health at Newcastle University, said: "This study shows that the conventional approach to somatic cell nuclear transfer is inefficient in humans.

"However, the authors were able to increase the efficiency by leaving the host oocyte [egg] genome in place.

"While this approach does not in itself provide a solution, it takes us a step closer to understanding where the problems lie."

No embryos required

Recently a different route to stem cells has been used. Instead of using an egg, a chemical bath "reprogrammes" an adult cell into a stem cell.

While this is seen as more ethical, there are concerns about whether such cells could be used therapeutically. There are differences between embryonic and "induced" stem cells, with the latter being more prone to expressing cancer causing genes.

Prof Robin Lovell-Badge, from the UK National Institute for Medical Research, said: "This paper will be seen as significant both by those who are trying to use somatic cell nuclear transfer to produce human patient-specific embryonic stem cell lines and by those who oppose human 'cloning' experiments."

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What makes a twin white or black?

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4 October 2011 Last updated at 08:10 GMT By Lucy Wallis BBC News Gene variants helped to determine Leo and Hope's different skin colour Genetically a mixed race and European couple, who are expecting twins, have about a one in 500 chance that the babies will have different skin colours. Fifty years ago these twin births were almost unheard of, but with the number of interracial relationships increasing, so too are the number of cases.

Around 12,000 sets of twins are born each year in Britain, but only a few are born with a very different skin colour to each other.

"When I think of the reality, I'm like 'that's my daughter there and she's got a totally different skin tone,' and it's just really bizarre that I created her," says Shirley Wales, who gave birth to non-identical twins.

Her son Leo has black skin and her daughter Hope, has white skin.

Shirley, who lives in West Yorkshire, is mixed race and the father of her twins is white. She describes her daughter as the "double" of her father, but is adamant that she should not forget her mixed race heritage.

"Her skin tone is white," she says, "but she is mixed race, and if I were to ever fill out a form, as much as she is white, it's 'no my daughter is mixed race,' because I want her to be proud."

Gene variants

In order to discover how this genetic phenomenon occurred, Shirley took a DNA test to find out more about her own genetic profile.

She was adopted when she was four years old, and her birth mother is Afro-Caribbean and her British birth father was white. Her DNA tests revealed that, genetically, she was exactly 50% African and 50% European.

This is very unusual, and the results suggested that Shirley's mother had pure African roots, and that her ancestors must have moved from Africa to the Caribbean quite recently.

On average Afro-Caribbean people are around one fifth European in their DNA, due to the history of mixed race births dating from the 17th Century and British colonialism in the Caribbean.

Shirley Wales took a DNA test to discover more about her own genetic profile

Dr Jim Wilson, a population geneticist at the University of Edinburgh, who analysed Shirley's test results, claims the difference in the skin colour of Shirley's twins can be attributed to her ancestry and the chance inheritance of different gene variants that Shirley carries.

"Our skin colour is determined by a number of gene variants - at least 20 variants, I would say, probably quite a few more than that," says Dr Wilson.

"Some of these we know, and some of them we don't yet know, and at each of these genes, that are influencing the colour of our skin, there tends to be two or more variants. One of which is producing a darker skin tone, and one of which is producing a lighter skin tone."

These gene variants control the amount of melanin or pigment produced in the skin. However the particular genes that a child inherits from their parents and ancestors is actually a chance process.

"I think of it as a deck of cards," says Dr Wilson. "Imagine you are at the casino and you have been dealt a hand of cards, some will be black, and some red. [Shirley] happened, by chance, to have passed more of the European skin colour variants, almost all of them, on to Hope, whereas more of the African ones, just by chance, on to Leo."

According to Dr Wilson, genetically a mixed race and European couple, who are expecting twins, have about a one in 500 chance that they are of different skin colours. This chance only applies to non-identical twins, because they are conceived from two eggs fertilised by two sperm.

As in a painter's palette, in the skin the presence of pigment dominates the absence of pigment, so the fact that Hope is white is very unusual.

Shirley's DNA test results also showed that she carries the gene for red hair, so there is the chance that Hope could be a red-head when she grows up.

'Vulnerability'

As well as the genetic differences, there are emotional and psychological factors to also consider.

Ebony and Moesha have very different personalities

Twelve-year-old Moesha from Glasgow struggles to fit in. She is white and her twin sister, Ebony and mother Stacey are black.

"I wish I was more like my mum," she says, "because she's a nice colour and I want to be the same colour as her."

Stacey feels that her daughter's difference in skin colour has had an affect on her self-esteem and body image.

"Moesha's got no confidence whatsoever, it's definitely all front," she says. "Ebony is very, very self-assured. What you see is what you get. Moesha puts on this act for everybody. Moesha is just that bit more vulnerable. She tries to fit in but I don't think she knows where she fits in."

Moesha was bullied at primary school for not being the same colour as her mother, which led to her feeling a sense of distinction from her family.

"She's said it before, 'I'm not part of this family, I'm not the same colour,'" says Stacey, "and I just tell her, 'you take your colouring from your dad.'"

'We're just brothers'

One in every 10 children in Britain is mixed race and this number is increasing all the time. The likelihood is that black and white twins could become more commonplace in society and not such a rarity.

"Social attitudes will evolve as this phenomenon increases," says Dr Wilson.

Wesley and Thomas have always stuck up for each other in life

Twin brothers, Thomas and Wesley Charnock, 29, from Manchester have been subjected to racism in their life because of their different skin tones.

Thomas, a naval airman, says his brother Wesley, who is white, has found it harder to deal with racist remarks, because people do not physically notice his mixed race parentage:

"It's like a hidden thing for him," says Thomas. "If someone was to look at him walking down the street, they wouldn't realise his mum was black and he has this African heritage. That's in my opinion why he gets more het up about it."

Wesley, an HGV driver, says that such racist comments are just "small mindedness".

"We're just brothers at the end of the day," he says, "and we don't think of ourselves as any different to anyone else."

Find out more in Twincredibles, which will be broadcast on Monday 10 October at 21:00 BST on BBC Two, as part of the Mixed Race Season.

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Flying Telescope Makes An Out-Of-This-World Find

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HEALTH MANAGEMENT. Guys, Quitting Smoking Makes It Bigger. Really.

Forget Viagra. A new study suggests that for firmer, faster erections, men should quit smoking. The researchers found that men who successfully kicked cigarettes had thicker, more rigid erections and reached maximal arousal five times faster than smokers who relapsed.
The study involved 65 sexually active male smokers who wanted to quit and were willing to have their erections measured in the lab. The participants were enrolled in an eight-week quit program, which involved using nicotine patches (and no other drugs) and counseling, and were brought in for erectile testing three times: before the quit date, halfway through the program, then again one month after the program's conclusion. To test men's erections, the researchers used a device called a penile plethysmograph, which measures changes in circumference and hardness, while the men watched porn.
Thirty-one percent of the men had successfully stopped smoking by the end of the study. Compared with men who relapsed, those who remained nicotine-free had wider, firmer erections and reached maximum sexual arousal (but, importantly, not climax!) much more quickly. These improvements were not seen, however, until after the men had stopped using the nicotine patches.
MORE: Study: A Mysterious Gene Variant That Makes Quitting Smoking Easier
Twenty percent of the participants reported having erectile dysfunction (ED) at the start of the study. By the end, 75% of these men who had quit smoking, no longer suffered erectile problems. But 61% of men with ED who had not stopped smoking also saw improvement in their condition. The difference between the two groups was not statistically significant, however, researchers said.
Despite the fact that the researchers' objective measurements showed improvements in sexual health among the quitters, there was no change in men's own ratings of their sexual functioning, including perceptions of arousal, orgasmic function and strength of erection.
"It might take longer for men to actually notice their level of difference subjectively outside of the lab, which is also dependent on their relationship with their sexual partner," study co-author Christopher Harte, of the VA Boston Healthcare System, told Reuters.
The current study isn't the first to connect smoking with sexual health. Smoking is known to damage blood vessels and hinder proper blood flow, which can also affect erectile function. Just this week, researchers from the Mayo Clinic found that men who made lifestyle changes to improve their cardiovascular health — by lowering cholesterol and blood pressure, losing weight and exercising — also improved their symptoms of ED.
The new findings, published in the British Journal of Urology International, suggest it's not just smoking, but nicotine itself that causes erectile problems, since improvements in men's erections weren't seen until after use of the patch was stopped.
The good news is that doctors may now have a new strategy to help people quit smoking. For many people, the long-term fear of cancer or heart disease isn't enough to motivate them to quit — or, worse, it can backfire by increasing stress and, in turn, the urge to smoke — but the promise of immediate and measurable improvements where it counts might be just the incentive male smokers need.
So, guys, the next time you have the urge to light up a post-coital Lucky, you might stop to think about whether it'll keep you from your next chance to crave one.

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