Gene identified that drives aggressive form of breast cancer

A team of researchers have identified a gene that drives one of the most aggressive forms of breast cancer. They hope that by finding a way to block the gene they may be able to make the cancer less aggressive.

The authors believe the most aggressive form of triple-negative breast cancer originates from stem cells.

In their study, published in Nature Communications, the researchers found that the gene known as "inhibitor of differentiation 4" (ID4) not only indicates a highly aggressive form of triple-negative breast cancer but also appears to control it.

"We found that ID4 is produced at high levels in roughly half of all triple-negative breast cancers, and that these cancers have a particularly poor prognosis," says project leader Dr. Alex Swarbrick. "We also showed that if you block the ID4 gene in experimental models of triple negative breast cancer, the tumor cells stop dividing."

Triple negative breast cancers are breast cancers that lackestrogen, progesterone and HER2 receptors. Breast cancers that have these receptors can be targeted by drugs.

Around 15% of all breast cancer cases are triple-negative breast cancers. Patients that develop them typically have a higher risk of recurrence and shorter survival than patients with other forms of breast cancer.

There appears to be a division among patients with triple-negative breast cancer; some patients succumb to the disease within 3-5 years while others can survive disease-free for much longer than many non-triple-negative breast cancer patients.

The researchers discovered a likely explanation for this differentiation in survival prospects - there are two distinct forms of triple-negative breast cancer, appearing to originate from different cell types.

While the more benign form of triple-negative breast cancer appears to originate from specialized cells, the team found that the aggressive form of the disease seems to originate from stem cells.

Could blocking ID4 make aggressive forms of breast cancer respond to tamoxifen?

Stem cells have the capacity to develop into a variety of different cell types in the body, and in many bodily tissues they divide to replenish other cells, providing the body with a form of internal repair. The manner in which stem cells are flexible and can spread into other tissues is similar to the way that many cancers operate.

Previous research has shown that breast stem cells are a vital part of breast growth and development during both puberty and pregnancy. The new study has now demonstrated that ID4 is responsible for determining whether these stem cells develop into specialist cells or not.

When ID4 is blocked in a stem cell, other genes that drive cell specialization are activated. In addition, the estrogen receptor and a number of other genes expressed by forms of breast cancer with better prognoses are also activated.

"Estrogen receptor-positive breast cancers have a relatively good prognosis because the drug tamoxifen is very effective at blocking the estrogen receptor and hence their growth," explains Dr. Swarbrick.

"We speculate, therefore, that by blocking ID4 it might be possible to turn stem-cell-like breast cancers into less aggressive breast cancers that may even respond to tamoxifen. If we are correct, that would be remarkable."

Following their discovery, the team will now investigate ID4 in order to work out the best strategy for blocking it in humans. They are also planning a mouse study to assess whether blocking ID4 can make tumors vulnerable to tamoxifen.

"We don't know yet whether we are seeing a real estrogen-dependent cancer after ID4 is blocked - one with an effective estrogen receptor - or just a caricature of one," states Dr. Swarbrick.

The team will be working in collaboration with a world expert on estrogen receptor function and studying these biochemical processes on a genome-wide scale as they attempt to fully understand the role that ID4 could play in the development and treatment of breast cancer.

Earlier this month, Medical News Today reported on a study finding that the shape of breast cancer cells can influence a tumor's response to treatment. Changing the shape of these cells could be a way of making them more sensitive to treatment.

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Stem cell-based therapy for type 2 diabetes shows promise

In a new study published in the journal Stem Cell Reports, researchers reveal how a combination of stem cell transplantation and antidiabetic medication successfully treated mice with type 2 diabetes.

This image shows the transplanted pancreatic beta cells derived from human embryonic stem cells.
Image credit: Jennifer Bruin, University of British Columbia

Senior study author Timothy Kieffer, of the University of British Columbia in Canada, and colleagues say the findings could lead the way for the first ever stem cell-based insulin replacement therapy being tested in humans with type 2 diabetes.

It is estimated that more than 29 million people in the US have diabetes. Type 2 diabetes accounts for around 90-95% of these cases. The condition occurs as a result of the body being unable to produce enough of the hormone insulin or use it effectively. This leads to high blood glucose levels.

In order to manage blood glucose levels, patients with type 2 diabetes are often treated with oral medication - such as metformin - insulin injections, or a combination of both. Kieffer and colleagues note, however, that such treatments can cause gastrointestinal problems, weight gain and low blood glucose levels, and some patients may not even respond to them.

With these factors in mind, the team tested a potential alternative treatment approach for patients with type 2 diabetes.

Improved glucose metabolism, insulin sensitivity with beta cell transplantation

The team created a mouse model of type 2 diabetes by inducing some markers of the disease in the animals - obesity, low response to insulin and high blood glucose levels - by feeding them a high-fat diet.

Next, the team transplanted mice with encapsulated pancreatic progenitor cells derived from human embryonic stem cells. These cells developed into fully-functioning beta cells - a type of cell in the pancreas that produces insulin - causing the mice to experience better glucose metabolism and an improvement in responsiveness to insulin.

What is more, mice that received stem cell transplantation in combination with antidiabetic medication experienced rapid weight loss, and - compared with either treatment alone - saw greater improvements in glucose metabolism.

Kieffer and colleagues now plan to test whether transplanting more mature beta cells into mouse models of type 2 diabetes - rather than pancreatic progenitor cells - could lead to faster alleviation of symptoms at a lower dose.

The researchers believe their approach could reach clinical trials in humans, particularly since a similar technique has recently been approved by the US Food and Drug Administration (FDA) and Health Canada for testing in patients with type 1 diabetes. Kieffer comments:

"Success in these clinical trials could pave the way for testing in patients with type 2 diabetes. Our hope is that a stem cell-based approach to insulin replacement will ultimately improve glucose control in patients with both type 1 and type 2 diabetes, resulting in healthier, longer lives."

Earlier this week, Medical News Today reported on a study by researchers from the University of East Anglia in the UK, in which they analyzed the global economic burden of type 2 diabetes.

The research reveals that patients with type 2 diabetes in the US have the highest lifetime health care costs related to the disease - at $283,000 - compared with countries that have similar average income levels.

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Future blindness cure? Stem cell success in lab

Scientists are one step closer to curing blindness, after they carried out the first successful transplant of light-sensitive photoreceptor cells from a synthetic retina that was grown from embryonic stem cells.
Researchers from University College London (UCL) and Moorfields Eye Hospital in the UK, transplanted the photoreceptor cells in to night-blind mice and found that the cells developed normally.
The cells integrated into the existing retina in the mice and formed the required nerve connections that transmit visual information to the brain.
The study, published in the journal Nature Biotechnology, shows embryonic stem cells could potentially be used to provide an "unlimited supply of healthy photoreceptors for retinal cell transplantations to treat blindness in humans."

The need for photoreceptor transplantations

Photoreceptors are light-sensitive nerve cells found in the retina of the eye. There are two types of photoreceptors - rods and cones.
The cones provide the eye's color sensitivity. The rods are not sensitive to color, but are more sensitive to light than the cones and are particularly important for providing the ability to see in the dark.

Researchers say this study is one more step towards treating blindness.

According to researchers, the loss of photoreceptors in the eye is a leading cause of sight loss in degenerative eye diseases such as retinitis pigmentosa, diabetes-related blindness and age-related macular degeneration.
Last year, the team conducted research that involved transplanting photoreceptors into mice suffering from retinal degeneration, using cells taken from healthy mice with normal sight.
However, the researchers say that this method of transplantation would "not be practical for the thousands of patients in need of treatment."
Back then, the researchers said: "We are hopeful that we will soon be able to replicate this success with photoreceptors derived from embryonic stem cells and eventually to develop human trials."
Professor Robin Ali, of the Institute of Ophthalmology at UCL and Moorfields Eye Hospital, told Medical News Today:
"Much of this work has been done in mice in the past. Photoreceptor precursor cells taken from the developing mouse retina and pumped into adult mice shows that this can be effective in restoring vision for the mice that lack vision. This really gave the framework for our translation program. To make it practical, we needed to find a cell source from which we can get these photoreceptor precursors."

"We have been working on trying to find ways of repairing the retina by transplanting photoreceptor cells, and we have demonstrated proof of concept of that development. They are not stem cells, they are not fully mature photoreceptor cells, but they are immature photoreceptor cells."

How was the synthetic retina grown?

The researchers say the new technique was developed using 3D culture and differentiation of mouse embryonic stem cells, a method recently developed in Japan.
Retinal precursor cells were grown using the 3D culture method and they were closely compared to normally developed cells, with the researchers noting different stages of development.
The researchers also carried out tests to ensure that the genes being expressed by the two types of cells were "biologically equivalent" to each other.
From this, the scientists were able to grow the synthetic retinas "in a dish" which contain all the nerve cells need to provide sight.
Prof. Ali explains:
"What we have been able to do is build on work of a Japanese group from a study a couple of years ago, in order to make a synthetic retina from embryonic stem cells. We have adapted that and we have shown for the first time that we can use embryonic stem cells to make a retina in a dish."

No more "three blind mice"

The researchers injected around 200,00 of the artificially grown cells into the retinas of the night-blind mice.

Professor Ali and his research team completed the first successful photoreceptor transplant using cells grown from a synthetic retina. Photo credit: UCL/MRC.

The study reports that three weeks after transplantation, the cells from the synthetic retina had "moved and integrated" within the the mice retina and began to look like "normal mature rod cells," which continued to be present after six weeks.
The researchers add that nerve connections (synapses) developed, meaning that the transplanted cells had the ability to connect with the existing connections within the retina.
Prof. Ali adds:
"This now means we have a cell source. This has all been done with mouse embryonic stem cells, but if we do it with human embryonic stem cells then we can do this for the first time using an embryonic stem cell source."
"That means we have got room to think about a human trial and repeat all this using human embryonic stem cells, and investigate whether we can repair the retina in conditions in which blindness is caused by loss of photoreceptor cells ."
Prof. Ali says that it will be a few years before this research will be used within a human trial, but the team have already started working with human embryonic stem cells.
He says:

"There are a number of ways that we can use this research to develop ways of treating blindness through gene therapy and artificial retinas. This is a very exciting approach because it has the ability to restore vision in patients who have very little vision, and the main cause of this in the developing world is loss of photoreceptors. Currently there is no treatment for that."

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Two Men HIV-Free After Bone Marrow Transplants

Two HIV-positive men no longer have detectable virus in their blood after receiving bone-marrow transplants to treat Hodgkin's lymphoma. Timothy Henrich and Daniel Kuritzkes , from Brigham and Women's Hospital, Boston, USA, explained at the International AIDS Society Conference, Kuala Lumpur, Malaysia, that one patient has been off HIV medications for over fifteen weeks and the other seven weeks, and there are still no signs of the virus rebounding.

Completely ridding a patient of HIV is extremely difficult. The virus hides within human DNA in such a way as to become "untouchable". ART (anti-retroviral therapy) helps control the virus in the bloodstream. However, as soon as ART stops, HIV usually replicates rapidly.

The two patients had been HIV-positive for over thirty years. They had both developed Hodgkin's lymphoma, a blood cancer that requires a bone marrow transplant if chemotherapy and other treatments failed. Blood cells are made in the bone marrow - experts believe the bone marrow is a major HIV reservoir.

After undergoing the bone marrow transplants, one man has had no detectable HIV in his blood for four years, and the other for two years.

Lead researcher, Dr. Timothy Henrich warned against using the C-word (cure), saying it is still early days.

In an interview with the BBC, Henrich said:

"We have not demonstrated cure, we're going to need longer follow-up. What we can say is if the virus does stay away for a year or even two years after we stopped the treatment, that the chances of the virus rebounding are going to be extremely low."

Last year, Kuritzkes and Henrich announced that HIV was easily detected in the blood lymphocytes of the two patients before their transplants, but within eight months post- transplant the virus had become undetectable. At the time the patients were still on ART.

The two patients came off ART earlier this year. They are regularly monitored and have no detectable HIV virus. Henrich said "We demonstrated at least a 1,000 to 10,000 fold reduction in the size of the HIV reservoir in the peripheral blood of these two patients. But the virus could still be present in other tissues such as the brain or gastrointestinal track."

If the virus were to rebound, it would mean that the brain, GI tract, lymph nodes or some other sites are important reservoirs of infectious virus "(and) new approaches to measuring the reservoir at relevant sites will be needed".

Bone marrow transplant not the answer to HIV infection

Bone-marrow transplant as a way of curing people infected with HIV is unlikely to ever become standard clinical practice.

In this case, the two patients had blood cancer; the transplants were performed to treat the cancer, not the HIV infection.

Most HIV-positive people do not have blood cancer. Bone marrow transplants are costly and risky - patients face a 20% risk of death. Before undergoing a transplant, the patient's immune system needs to be weakened to minimize the risk of rejection.

A third patient, who also had lymphoma and was HIV-positive and had received the same transplant as the two Boston subjects, died from cancer.

With ART, a person with HIV can enjoy the same life expectancy as other people.

Doctors "cured" baby born with HIV infection

In March this year, doctors from Johns Hopkins Children's Center, the University of Mississippi Medical Center and the University of Massachusetts Medical School announced that an HIV-positive baby who was administered ART within 30 hours of being born had been "cured".

Deborah Persaud, M.D., explained that it is very uncommon to treat a baby for HIV-infection so soon after birth. She added that this was the first case of a functional cure in an HIV-positive infant. The medical team believes that the prompt administration of antiretroviral therapy led to the newborn's cure.

Dr. Persaud said "Prompt antiviral therapy in newborns that begins within days of exposure may help infants clear the virus and achieve long-term remission without lifelong treatment by preventing such viral hideouts from forming in the first place."

First apparent HIV-infection cure probably occurred in Germany, 2010

In December 2010, researchers from Charite - University Medicine Berlin, Germany, wrote in the journal Blood than an acute myeloid leukemia patient, Timothy Brown, who was also HIV-positive had been cured of HIV infection after receiving a bone marrow transplant.

The scientists wrote "Our results strongly suggest that cure of HIV has been achieved in this patient."

In 2007 Timothy Brown stopped receiving ART, had his own immune system effectively wiped out with high-dose chemotherapy and radiation therapy, and received a bone marrow transplant.

In this case, the donor had a very rare gene mutation - CCR5-delta32 - which protected him from HIV infection, meaning that Brown acquired that protection. In July 2012, scientists in California found traces of HIV in his tissue. However, Brown says that any virus that remains in his body is completely inactive ("dead") and cannot replicate.

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Type 1 Diabetes Stem Cell Breakthrough Moves Toward Cure

In a breakthrough that signifies a move toward a cure for type 1 diabetes, researchers in Australia have identified stem cells in the pancreas that can be turned into insulin-producing cells. The finding promises to bring closer the day when people with type 1 diabetes will be able to produce their own insulin in their own regenerated insulin-producing pancreatic cells.

The discovery is the work of scientists at the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria. They write about their findings in a paper published online in PLoS ONE on 9 November.

Type 1 Diabetes

Type 1 diabetes is a disease where the body's immune system attacks and destroys the cells in the pancreas that produce insulin. Without insulin the body cannot control blood sugar or glucose, which results in serious damage to organs and potentially fatal levels of blood glucose.

Patients with type 1 diabetes have to have several injections of insulin a day, or use an insulin infusion pump, to control their blood glucose. But these methods are not perfect and patients remain at risk of serious long-term health problems.

Pinpointed Cell of Origin

In their paper, Dr Ilia Banakh and Professor Len Harrison from the Walter and Eliza Hall Institute's division of Molecular Medicine, and colleagues, describe how they identified and isolated stem cells from the adult pancreas, and then developed a way to coax them into insulin-producing cells that can secrete insulin in response to glucose.

This discovery could lead to new treatments that mean daily insulin injections become a thing of the past.

Harrison explains in a separate statement how there have been previous successes at generating insulin-producing cells in the adult pancreas from cells with "stem-like" features, but what excites him about this find is that Banakh has pinpointed "the cell of origin of the insulin-producing cells and shown that the number of these cells and their ability to turn into insulin-producing cells increases in response to pancreas injury".

The researchers worked first with cells in the "test tube", and then tested the method in mice:

"Insulin expression was maintained when tissue was transplanted within vascularised chambers into diabetic mice," they write.

Implications

The researchers believe their discovery provides further evidence that stem cells don't only occur in the embryo and means people with type 1 diabetes may one day be able to regenerate their own insulin-producing cells.

The finding means the potential to regenerate insulin-producing cells is present in all of us, even as adults, says Harrison, a clinician scientist whose work is recognized this month as Diabetes Australia confers the Outstanding Contribution to Diabetes Award on him to mark World Diabetes Day on Thursday 14 November.

"In the long-term, we hope that people with type 1 diabetes might be able to regenerate their own insulin-producing cells. This would mean that they could make their own insulin and regain control of their blood glucose levels, curing their diabetes," declares Harrison, adding the proviso:

"Of course, this strategy will only work if we can devise ways to overcome the immune attack on the insulin-producing cells, that causes diabetes in the first place."

Funds from the JDRF, the National Health and Medical Research Council of Australia and the Victorian Government helped finance the study.

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Cancer-Killing Stem Cells Could Be Used To Treat Cancer

Researchers in Japan have for the first time shown it is possible to make cancer-specific immune system cells from induced pluripotent stem cells (iPSCs). Their work brings closer the day when therapies use cloned versions of patients' own cells to boost their immune system's natural ability to kill cancer cells.

The researchers, from the RIKEN Research Centre for Allergy and Immunology in Yokohama, describe how they created cancer-specific killer T lymphocytes from iPSCs, in a paper published online on 3 January in the journal Cell Stem Cell.

Hiroshi Kawamoto and colleagues started with mature T lymphocytes specific for a certain type of skin cancer and reprogrammed them into IPSCs with the help of "Yamanaka factors". The iPSCs cells then generated fully active, cancer-specific T lymphocytes.

Yamanaka factors are named after Shinya Yamanaka, who with British scientist John B. Gurdon, won the 2012 Nobel Prize for Physiology or Medicine for discovering that mature cells can be reprogrammed to become pluripotent stem cells.

Yamanaka discovered that treating adult skin cells with four pieces of DNA (the Yamanaka factors) makes them revert back to their pluripotent state, where they have the potential, almost like embryonic stem cells, to become virtually any cell in the body.

Scientists have created cancer-specific immune system cells that could be capable of killing cancer cells.

Speaking about their breakthrough in making cancer-specific T cells, Kawamoto says in a statement:

"We have succeeded in the expansion of antigen-specific T cells by making iPS cells and differentiating them back into functional T cells."

Previous attempts using conventional methods to make cancer-killing T lymphocytes in the lab have not been very successful. The cells failed to kill the cancer cells, mainly because they did not live long enough.

So Kawamoto and colleagues thought they would have more success if they went down the iPSC route.

After making a batch of iPSCs by exposing melanoma-specific mature T lymphocytes to the Yamanaka factors, they grew them in the lab and coaxed them to differentiate into killer T lymphocytes again.

"In this study, we established iPSCs from mature cytotoxic T cells specific for the melanoma epitope MART-1," they write.

They showed that the new batch of T lymphocytes was specific for the same type of melanoma as the original lymphocytes.

The new cells kept the same genetic structure that enabled them to express the cancer-specific receptor on their surfaces: "more than 90% of the resulting cells were specific for the original MART-1 epitope," note the researchers.

They also showed that the new T lymphocytes were active and able produce the anti-tumor compound interferon-gamma when exposed to antigen-presenting cells.

Kawamoto and colleagues are now planning to test whether the new T cells can selectively kill tumor cells without harming healthy cells.

"If they do, these cells might be directly injected to patients for therapy. This could be realized in the not-so-distant future," says Kawamoto.

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Broken Bones Mended With Stem Cells And Plastic

New bone tissue grown from patients' own stem cells that attach themselves to an implanted, rigid lightweight plastic "scaffolding" which gradually degrades and is replaced as new bone grows, could soon be healing shattered limbs, according to a new research report.

The degradable polymer material is the result of a seven-year collaboration between the Universities of Southampton and Edinburgh. The researchers report their work in a paper published in the journal Advanced Functional Materials.

In their background information they note how bone tissue regeneration is often needed after trauma, where "substantial bone or cartilage loss may be encountered", and this drives researchers to develop new biomaterials, especially those that can form a 3D structure.

Their new material is "strong enough to replace bone and is also a suitable surface upon which to grow new bone," says study author Mark Bradley, a professor in the University of Edinburgh's School of Chemistry, in a statement.

Using what the statement describes as a "pioneering technique", Bradley and colleagues created and experimented with hundreds of candidates before settling on a material that was robust, lightweight, and able to support bone stem cells.

The new technique, called "solvent blending", is a process that "avoids complications associated with conventional thermal or mechanical polymer blending or synthesis, opening up large areas of chemical and physical space, while potentially simplifying regulatory pathways towards in vivo application," they write.

The material they finally settled on is a polymer blend of three types of manmade and natural plastics and can be inserted into broken bones to encourage real bone to re-grow.

The polymer blend is like a scaffold made of honeycomb that allows blood to flow through it. Stem cells from the patient's bone marrow that are in the blood attach themselves to the scaffold and grow new bone tissue.

As time goes on, the material degrades, allowing the re-grown bone to replace it.

The researchers have already tested it in the lab and in animals, and are now looking to move into human clinical testing.

Bradley says:

"We are confident that this material could soon be helping to improve the quality of life for patients with severe bone injuries, and will help maintain the health of an ageing population."

His colleague and co-author Richard Oreffo, Professor of Musculoskeletal Science at the University of Southampton, says:

"Fractures and bone loss due to trauma or disease are a significant clinical and socioeconomic problem. This collaboration between chemistry and medicine has identified unique candidate materials that support human bone stem cell growth and allow bone formation. Our collaborative strategy offers significant therapeutic implications."

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Queen's Study Aims To Use Stem Cells To Help Save Sight Of Diabetes Sufferers

Scientists at Queen's University Belfast are hoping to develop a novel approach that could save the sight of millions of diabetes sufferers using adult stem cells.

Currently millions of diabetics worldwide are at risk of sight loss due to a condition called Diabetic Retinopathy. This is when high blood sugar causes the blood vessels in the eye to become blocked or to leak. Failed blood flow harms the retina and leads to vision impairment and if left untreated can lead to blindness.

The novel REDDSTAR study (Repair of Diabetic Damage by Stromal Cell Administration) involving researchers from Queen's Centre for Vision and Vascular Science in the School of Medicine, Dentistry and Biomedical Sciences, will see them isolating stem cells from donors, expanding them in a laboratory setting and re-delivering them to a patient where they help to repair the blood vessels in the eye. This is especially relevant to patients with diabetes were the vessels of the retina become damaged.

At present there are very few treatments available to control the progression of diabetic complications. There are no treatments which will improve glucose levels and simultaneously treat the diabetic complication.

The €6 million EU funded research is being carried out with NUI Galway and brings together experts from Northern Ireland, Ireland, Germany, the Netherlands, Denmark, Portugal and the US.

Professor Alan Stitt, Director of the Centre for Vision and Vascular Science in Queen's and lead scientist for the project said: "The Queen's component of the REDDSTAR study involves investigating the potential of a unique stem cell population to promote repair of damaged blood vessels in the retina during diabetes. The impact could be profound for patients, because regeneration of damaged retina could prevent progression of diabetic retinopathy and reduce the risk of vision loss.

"Currently available treatments for diabetic retinopathy are not always satisfactory. They focus on end-stages of the disease, carry many side effects and fail to address the root causes of the condition. A novel, alternative therapeutic approach is to harness adult stem cells to promote regeneration of the damaged retinal blood vessels and thereby prevent and/or reverse retinopathy."

"This new research project is one of several regenerative medicine approaches ongoing in the centre. The approach is quite simple: we plan to isolate a very defined population of stem cells and then deliver them to sites in the body that have been damaged by diabetes. In the case of some patients with diabetes, they may gain enormous benefit from stem cell-mediated repair of damaged blood vessels in their retina. This is the first step towards an exciting new therapy in an area where it is desperately needed."

The research focuses on specific adult stem-cells derived from bone-marrow. Which are being provided by Orbsen Therapeutics, a spin-out from the Science Foundation Ireland-funded Regenerative Medicine Institute (REMEDI) at NUI Galway.

The project will develop ways to grow the bone-marrow-derived stem cells. They will be tested in several preclinical models of diabetic complications at centres in Belfast, Galway, Munich, Berlin and Porto before human trials take place in Denmark.

Queen's Centre for Vision and Vascular Science is a key focus of the University's ambitious £140m 'together we can go Beyond' fundraising campaign. It is due to expand its Vision Sciences programme further when the University's new £32m Wellcome-Wolfson Centre for Experimental Medicine opens in 2015. Along with vision, two new programmes in Diabetes and Genomics will also be established in the new Centre which is set to stimulate additional investment, lead to further global collaborations and create more opportunities for new health and biotech companies in Northern Ireland.

Further information on the Centre for Vision and Vascular Science at Queen's is available online at http://www.qub.ac.uk/research-centres/CentreforVisionandVascularScience/

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Revolutionary Stem Cell Treatment Repairs Spinal Cord Injuries In Paralyzed Dogs

Scientists have used a special cell to regenerate damaged parts of dogs' spines. Researchers are cautiously excited about these results which could potentially have a future role in the treatment of human patients with similar spinal injuries.

For many years, scientists have been aware that olfactory ensheathing cells (OEC) could be helpful in treating the damaged spinal cord because of their distinctive properties. The unique cells have the capacity to support nerve fiber growth that preserves a pathway between the nose and the brain.

Earlier studies consisting of laboratory animals have shown that OECs can be helpful in regeneration of the parts of nerve cells that pass on signals (axons). OECs were used as a bridge linking damaged and undamaged tissues in the spinal cord. A Phase 1 trial in humans with spinal cord injuries has determined that the procedure is safe.

The current study, published in the journal Brain, is the first double-blinded, randomized, controlled study to examine the effectiveness of these transplants to increase function in spinal cord injuries. The trial used animals with spontaneous and accidental spinal cord injuries. This method resembled closely the way the procedure could potentially work for human patients.

The study included 34 dogs that all suffered critical spinal cord injuries (SCIs). A year or more after the injury, the dogs were without the ability to use their legs and were unable to feel pain in their hind legs and adjoining areas.

Researchers say that paralysis was reversed in Jasper the dachshund using cells grown from the lining of his nose.

 

 

Several of the dogs were dachshunds, who are extremely prone to this type of injury. Dogs in general are more likely to experience SCIs because they can be caused by a slipped disc, which is normally a minor injury in humans.

One group involved in the study received OECs from the lining of their own nose injected into the injured area. The other group of dogs were injected with only the liquid in which the cells were transplanted. The researchers and the owners were both in the dark about which dogs received which type of injections.

The dogs were analyzed for adverse reactions during a 24 hour period before being returned to their owners. After that, they were tested every month for neurological function and to have their walking manner assessed on a treadmill while being supported in a harness. Specifically, the researchers watched to see if the dogs could coordinate the movement of their front and back legs.

The groups of dogs that received the OEC injection had significant improvement that was not present in the other group. The OEC injection group was able to move previously paralyzed legs and coordinate these movements with their front quarters.

This suggests that in these particular dogs, neuronal messages were being relayed across the formerly damaged part of the spinal cord. The researchers found that the new nerve connections causing this recovery were happening over short distances within the spinal cord and not among long distances needing the brain to connect with the spinal cord.

Professor Robin Franklin, a co-author of the study from the Welcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, said:

"Our findings are extremely exciting because they show for the first time that transplanting these types of cell into a severely damaged spinal cord can bring about significant improvement.

We're confident that the technique might be able to restore at least a small amount of movement in human patients with spinal cord injuries but that's a long way from saying they might be able to regain all lost function. It's more likely that this procedure might one day be used as part of a combination of treatments, alongside drug and physical therapies, for example."

The authors emphasize that human patients with a spinal cord injury rate a restoration in sexual function and continence much greater than better mobility. Some dogs in the study got back their bowel and bladder control but the number was not satistically exceptional.

Dr Rob Buckle, Head of Regenerative Medicine at the MRC, commented:

"This proof of concept study on pet dogs with the type of injury sustained by human spinal patients is tremendously important and an excellent basis for further research in an area where options for treatment are extremely limited. It's a great example of collaboration between veterinary and regenerative medicine researchers that has had an excellent outcome for the pet participants and potentially for human patients."

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