By Malcolm Ritter

For the first time, scientists have improved hearing in deaf animals by using human embryonic stem cells, an encouraging step for someday treating people with certain hearing disorders.

"It's a dynamite study (and) a significant leap forward," said one expert familiar with the work, Dr Lawrence Lustig of the University of California, San Francisco.

The experiment involved an uncommon form of deafness, one that affects fewer than 1 percent to perhaps 15 percent of hearing-impaired people. And the treatment wouldn't necessarily apply to all cases of that disorder. Scientists hope the approach can be expanded to help with more common forms of deafness. But in any case, it will be years before human patients might benefit.

Results of the work, done in gerbils, were reported online Wednesday in the journal Nature by a team led by Dr Marcelo Rivolta of the University of Sheffield in England.

To make the gerbils deaf in one ear, scientists killed nerve cells that transmit information from the ear to the brain. The experiment was aimed at replacing those cells.

Human embryonic stem cells can be manipulated to produce any type of cell. Using them is controversial because they are initially obtained by destroying embryos. Once recovered, stem cells can be grown and maintained in a lab and the experiment used cells from lab cultures.

The stem cells were used to make immature nerve cells. Those were then transplanted into the deaf ears of 18 gerbils.

Ten weeks later, the rodents' hearing ability had improved by an average of 46 percent, with recovery ranging from modest to almost complete, the researchers reported.

And how did they know the gerbils could hear in their deafened ears? They measured hearing ability by recording the response of the brain stem to sound.

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Human stem cells help deaf animals

Embryonic stem cells have been dubbed "the sleeper issue" of the 2012 election, but stem-cell research (taking cells from human embryos to create new cells that can treat disease) has long been a hot-button topic. The problem is that embryos traditionally are destroyed to extract the cells--something that plenty of people are uncomfortable with. But if there was a way to extract human embyronic stem cells without destroying anything, well, that shouldnt create any ethical quandaries. Advanced Cell Technology, a biotechnology company specializing in cellular therapies, thinks it has the solution.

ACT uses an embryonic stem-cell-removal technique that doesnt destroy anything: It removes a single cell from embryos that are in the eight-cell stage--in other words, extremely early on. Its identical to whats done in in-vitro fertilization clinic for genetic testing of diseases like Tay-Sachs and Huntingtons Disease. "Its a non-destructive, non-harmful method of extracting these cells and creating embryonic stem cells. There are thousands of babies born every year having this exact kind of genetic testing done," says ACT CEO Gary Rabin.

The cells propagate infinitely, so once you have what you need, you never have to go back to an in-vitro fertilization clinic to get more. ACT hasnt taken cells from a clinic since 2005.

The technique is just part of the battle, of course; creating viable medical treatments is also necessary to prove ACTs worth. Despite a history of financial mismanagement--when Rabin joined the company in 2010, it had less than $1 million in the bank (now it has over $10 million)--ACT has some exciting developments coming down the pike.

Most of them have to with the eye, which is an ideal place to start for embryonic stem cell treatment: The subretinal space in the eye is immune-privileged, meaning there shouldnt be any issues with immune system rejection; everything you do in the eye can be observed down to the cellular level thanks to advanced scanning techniques; and there are 15 million patients in the U.S. with age-related macular degeneration (AMD)--a number that is expected to double over the next 20 years as the population ages. There are no real cures or therapies for AMD, and most drugs used in the eye were developed in the 1960s. Its a space thats ripe for change.

ACT is running three phase 1 clinical trials: a U.S. trial of an AMD treatment, and two trials (one in the U.S. and one in the U.K.) with a treatment for Stargardts Macular Dystrophy (SMD), a juvenile disease that causes progressive vision loss, ultimately leading to blindness. The trials have been promising so far.

"All of the [11] patients [in the three trials] treated long enough to have any effect have had subjective improvements in visual acuity, and nearly all have had measurable improvement in visual acuity," says Rabin. "We didnt expect that in this patient population. As this is a phase 1 study, were treating very late stage patients." The three trials are still ongoing, but ACT is on to thinking about how to design phase 2. "Its clear now that we dont have any safety issues with these cells," explains Rabin.

How do the stem cells get implanted in the first place? You start with an embryonic stem-cell line, and through culturing media and differentiation techniques turn them into retinal pigment epithelium (RPE)--cells that are critical for visual function. When RPE cells die because of old age or other causes, theres a corresponding decline in vision. So ACTs technique is to inject RPE cells into the back of the eyes retinal space. "The cells are injected in a suspension of a proprietary media thats more or less like a saline," says Rabin.

ACTs main focus is on its eye treatments, but the company is also looking at the potential to use mesenchymal stem cells (MSCs), a kind of cell that can turn into a variety of cell types, to treat autoimmune disorders like multiple sclerosis and lupus. There are hundreds of clinical trials involving MSCs that are going on right now, but "the usefulness in earlier-stage cells give us a very significant advantage in terms of treating these kinds of diseases," says Rabin.

Right now, at least, ACT says it hasnt experienced too much pushback for its methods. "The problem is in this political climate its a hot button issue. If you raise it with any Republican candidate, its 'Oh, you destroy embyronic stem cells, youre killing babies.' Its just a convenient headline," says Rabin. "Theres a lot of education we have to do to make people aware of how this [works]."

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The Company That Can Generate Medical Treatments From Embryonic Stem Cells Without Pissing Anyone Off

As a potential method for producing cells to repair failing systems in human bodies, many scientists are looking to stem cells cells that have the power to differentiate or transform into many different cell types. Scientists already know how to extract stem cells from adult human fat and hope they will someday be able to take a persons own cells and develop the tissues they need.

But there is a major constraint to this plan out of all the cells drawn from adult fat, only a small percentage can successfully turn into the desired cell type. Some could even turn into harmful cell types. To tackle this challenge, Eric Darling, assistant professor of biology, and his lab are working to produce two methods to sort the useable cells from the chaos.

Youre reliant on these cells, said Hetal Desai GS, lead researcher on one of the projects. If youre trying to grow a bone, youre reliant on how well the cells going to respond to (the chemical stimulus), how well theyre going to accomplish turning into (something like) bone. So if you have a bunch of cells that are essentially going to just hang out and not do anything, thats bad. If you can weed those out and keep the ones that are optimal thats where these techniques really have a lot of power. Desais research, published Sept. 5, focused on developing a probe that would light up when stem cells were transforming into the correct cell type. The labs other recent project in the area took a different tack measuring the physical properties of cells to see their potential to turn into bone, cartilage or fat.

Glowing beacons When a stem cell is differentiating, it sends messenger RNA signals that produce specific proteins and help it transform. Darlings team created a probe that binds to specific RNA and lights up showing when specific cells are beginning to differentiate specifically into bone.

We were basically able to quantify, in living cells and in real time, how many of these cells are expressing the genes at different stages of turning into bone, Desai said. She started work on the project while she was on rotation in Darlings lab and stayed on to make it a main research focus.

The probe, which was developed in 1996 and can be designed to respond to any specific gene, was dispatched into two groups of stem cells derived from fat one which had been treated by a chemical to induce differentiation into bone and one that had not. Looking at the cells, an observer could immediately tell by the glow which cells were responding positively to the chemical signals. Over the course of three weeks, the group watched the waves of fluorescence mark the different stages in the cells transformations.

Desai said the hardest part of the study was designing the probe. We needed it to be a fly on the wall of the process, she said. We didnt want it to interfere with the cell, but we wanted to make sure we had a really clear signal that we could assess really easily. The team designed the probe to only interface with the specific RNA that indicated differentiation, and they ran several experiments to ensure the probe was not blocking the cells from using the RNA normally.

Eventually, the researchers hope the probe can be used to pick out cells responding well to the chemical signals in a clinical setting, providing a mechanism for sorting between cells. Richard Freiman, associate professor of biology at Brown who was not involved in the study, called this the most exciting aspect of the research.

In thinking about therapy, measuring changes on those cells before you actually put them back into a patient is absolutely essential, he said. Its rare to be able to do that with living cells if one can, its very powerful.

A predictive approach In addition to developing the molecular probe, Darlings lab tackled the sorting from a predictive angle in a study published this May. The idea came to Darling during his post-doctorate at Duke University, when he used an atomic force microscope to examine the physical properties of cells. Darling said he found that stem cells had a wide variation and wondered whether that variation could predict the cells ability to turn into different kinds of tissue.

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Biology prof finds methods of identifying usable stem cells

SAN DIEGO--(BUSINESS WIRE)--

This week in the journal Scientific Reports (Nature Publishing Group), scientists from Allele Biotechnology describe an important advance in the generation of stem cells capable of producing all the different tissues of the human body. In an article entitled Feeder-Free Derivation of Human Induced Pluripotent Stem Cells with Messenger RNA, Alleles scientists present the fastest and safest method yet for converting ordinary human skin cells into induced pluripotent stem cells (iPSCs).

The scientific efforts were led by Dr. Luigi Warren, whose pioneering work on footprint-free reprogramming using messenger RNA was the foundation for Alleles breakthrough. Through the united efforts of Dr. Warren and the scientists at Allele Biotechnology, his technique was re-engineered to increase cell conversion efficiency and eliminate any use of potentially unsafe reagents, while substantially reducing the time and effort needed to make stem cells. Dr. Warren believes that because of its advantages this technology should become the method of choice for iPSC cell banking.

According to Dr. Jiwu Wang, corresponding author on the paper and CEO of Allele Biotechnology, This advance in stem cell derivation will enable both fundamental scientific research and clinical applications which has been the mission of Allele Biotechnology from its inception.

Allele Biotechnology and Pharmaceuticals Inc. is a San Diego-based biotechnology company that was established in 1999 by Dr. Jiwu Wang and colleagues. A research based company specializing in the fields of RNAi, stem cells, viral expression, camelid antibodies and fluorescent proteins; Allele Biotechnology has always striven to offer products and services at the cutting edge of research.

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Allele Biotechnology Announces New Advance in Production of Human Stem Cells

Researchers have found a way to use human embryonic stem cells to restore hearing to gerbils. Specifically, they were able to repair damage to the nerve that connects the inner ear to the brain, as they reported in Naturethis week. This type of hearing loss, which affects many people, is currently untreatable; it isnt helped by hearing aids or cochlear implants, both of which depend on the auditory nerve to send the final signals to the brain. Applied to humans, this research could perhaps help a group that are currently without treatment for hearing loss.

By bathing human embryonic stem cells in certain chemicals, the researchers turned the cells into the precursors of auditory nerve cells, something they already knew how to do. They then transplanted these precursor cells into gerbils whose auditory nerves had been disabled by a poison. After 10 weeks, the transplanted stem cells had repaired the broken connection between the ear and the brain, and the gerbils hearing improved by nearly 50 percent.

It could take 15 years for such research to translate to treatments for humans, Stefan Heller, a stem cell researcher not involved in the study but also working on treatments for hearing loss, told Nature Newsif the research makes that leap. Theres no guarantee that the technique will work as well in humans as it does in gerbils. Keep your ears pricked up for further progress on this front.

Gerbil photo courtesy of Eschold/Wikimedia Commons

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Human Stem Cells Repair Hearing Loss in Gerbils | 80beats

Sept. 15, 2012, midnight

A GERMAN shepherd is the Borders first pet to have stem-cell therapy.

The three-year-old has a painful congenital joint condition called osteo-chondrosis that has led to arthritis.

After surgery and other therapies fell short, owners Nick and Myfanwy Magelakis investigated alternatives to give Rolf a chance to be a normal animal,

Stem-cell therapy doesnt come cheap each treatment costs $500 a dose, excluding the cost of anaesthetic and vet charges.

But Dr Magelakis, an Albury dentist, said he was philosophical about the hefty bill.

Although humans technically have dominion over this planet, we have a duty to look after animals and care for them, Dr Magelakis said yesterday.

Its heartbreaking to see a dog not being able to walk, yelping in pain and looking up at you for help.

Stem cells were injected into both of Rolfs knees this week in what was a straight-forward day procedure at Alburys Family Vet Centre.

Veterinarian Nadine Miller said while scientists were still learning how stem cells worked, they knew they stimulate healing of the joint by helping new connective tissue to form.

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Stem cells to ease pet pain