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Natural hydrogel may boost spinal cord healing

September 19, 2009 By admin Leave a Comment

Washington, Sep 18 (ANI): A jab of biomaterial gel into a spinal cord injury site may significantly improve healing, according to researchers at the Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center.

Dr. Mark Preul and Dr. Alyssa Panitch have found in a study that injection of an engineered hydrogel made up mainly of hyaluronic acid (a naturally-occurring body substance) into the spinal cord injury site decreases scarring, and promotes a realignment of the spinal cord fibres around the injury site.

The hyaluronic acid, which forms a scaffold-like configuration may help to structurally stabilize the spinal cord injury site.

The researchers traced cells in the brain stem after injury, and found much higher levels in the hydrogel treated animals as compared to animals that did not receive the treatment, and approached nearly normal levels.

Treated animals had higher functional scores than their non-treated counterparts.

“Spinal cord injury is devastating to civilian and military populations – especially to the young. There has been little progress toward paradigms of regeneration and few results that show real, sustained functional recovery. We’ve been so pre-occupied with regeneration, but that is a highly complicated and difficult to define goal. This project is a synergy of neurosurgeons and bioengineers that attempts repair of the SCI lesion cavity using a tissue-engineering biomaterials approach,” says Preul.

He added that the team aimed at finding ways to structurally allow the body to better heal itself.

“In this project we did not add anything to the hyaluronic acid. It may be that adding growth factors or cells into the gel matrix may allow even better results,” he said.

Preul said that the results show “we may be on a practical path that can give hope to the many people who suffer this sort of injury.”

The work was presented at the Annual Meeting of the American Association of Neurological Surgeons in San Diego where it won the Synthes Prize for Spine Research. (ANI)

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Stem cell transplantation may correct rare genetic disorder in kids

September 19, 2009 By admin Leave a Comment

Washington, Sep 18 (ANI): Scripps Research Institute scientists have offered new hope for parents whose children suffer from the rare genetic disorder ‘cystinosis’ by showing through an experiment on mice that stem cell transplantation can successfully correct the defect.

“After meeting the children who suffer from this disease, like an 18-year-old who has already had three kidney transplants, and the families who are desperately searching for help, our team is committed to moving toward a cure for cystinosis, a lysosomal storage disorder. This study is an important step toward that goal,” said principal investigator Stephanie Cherqui.

In the study, the researchers used bone marrow stem cell transplantation to address symptoms of cystinosis in a mouse model.

The procedure virtually halted the cystine accumulation responsible for the disease, and the cascade of cell death that follows.

Cystine is a by-product of the break down of cellular components the body no longer needs in the cell’s “housekeeping” organelles, called lysosomes.

Normally, cystine is shunted out of cells, but in cystinosis a gene defect of the lysosomal cystine transporter causes it to build up, forming crystals that are especially damaging to the kidneys and eyes.

Cystinosis is a rare but devastating disease affecting children as young as six months, who begin to suffer renal dysfunction, which grows progressively worse with time. Other symptoms include diabetes, muscular disease, neurological dysfunction, and retinopathy.

The only available drug to treat cystinosis, cysteamine, while slowing the progression of kidney degradation, does not prevent it, and end-stage kidney failure is inevitable.

In the new study, the researchers found that transplanted bone marrow stem cells carrying the normal lysosomal cystine transporter gene abundantly engrafted into every tissue of the experimental mice.

This led to an average drop in cystine levels of about 80 percent in every organ.

Not only it prevented kidney dysfunction, there was less deposition of cystine crystals in the cornea, less bone demineralization, and an improvement in motor function.

“The results really surprised and encouraged us. Because the defect is present in every cell of the body, we did not expect a bone marrow stem cell transplant to be so widespread and effective,” says Cherqui.

Cherqui said that adult bone marrow stem cell therapy is particularly well suited as a potential treatment for cystinosis because these cells target all types of tissues.

In addition, stem cells reside in the bone marrow for the duration of a patient’s life, becoming active as needed, a particular benefit for a progressive disease like cystinosis.

The study has been published in the journal Blood. (ANI)

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Popular diabetes drug may help fight breast cancer

September 15, 2009 By admin Leave a Comment

Washington, Sept 15 (ANI): A popular diabetes drug called metformin has been found to be effective in fighting breast cancer.

The findings of the study from Harvard Medical School showed that metformin, along with conventional chemotherapy, shows promise for treating and delaying recurrence of breast cancer.

“We have found a compound selective for cancer stem cells,” said senior author Kevin Struhl, the David Wesley Gaiser professor of biological chemistry and molecular pharmacology at HMS.

“What’s different is that ours is a first-line diabetes drug,” he added.

The drug seemed to work independently of its ability to improve insulin sensitivity and lower blood sugar and insulin levels, all of which are also associated with better breast cancer outcomes.

“There is a big desire to find drugs specific to cancer stem cells,” said Struhl.

“The cancer stem cell hypothesis says you cannot cure cancer unless you also get rid of the cancer stem cells. From a purely practical point of view, this could be tested in humans. It’s already used as a first-line diabetes drug,” he added.

Lead researchers Heather Hirsch and Dimitrios Iliopoulos found that the combination of metformin and the cancer drug doxorubicin killed human cancer stem cells and non-stem cancer cells in culture.

In mice, pre-treatment with the diabetes drug prevented the otherwise dramatic ability of human breast cancer stem cells to form tumours.

In cases where tumours were allowed to take hold for 10 days, the dual therapy also reduced tumour mass more quickly and prevented relapse for longer than doxorubicin alone.

“This is an exciting study,” said Jennifer Ligibel, a medical oncologist at Dana-Farber Cancer Institute and an HMS instructor in medicine, who was not involved in the study.

“There is a lot of interest in studying metformin in breast cancer, but so far we do not have direct evidence that metformin will improve outcomes in patients,” Ligibel said. “That’s what this trial is for.”

The findings appear online in the journal Cancer Research. (ANI)

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Master gene that switches on disease-fighting cells identified

September 14, 2009 By admin Leave a Comment

London, Sep 14 (ANI): British scientists have identified the master gene, called E4bp4, that causes blood stem cells to turn into disease-fighting ‘Natural Killer’ (NK) immune cells.

The discovery, by researchers at Imperial College London, UCL and the Medical Research Council’s National Institute for Medical Research, could one day help scientists boost the body’s production of these frontline tumour-killing cells, creating new ways to treat cancer.

By ‘knocking out’ E4bp4 in a mouse model, the researchers created the world’s first animal model entirely lacking NK cells, but with all other blood cells and immune cells intact.

The breakthrough model should help solve the mystery of the role that Natural Killer cells play in autoimmune diseases, such as diabetes and multiple sclerosis.

According to many scientists, these diseases are a result of malfunctioning NK cells that turn on the body and attack healthy cells, which cause disease instead of fighting it.

They believe that clarifying NK cells’ role could lead to new ways of treating these conditions.

Natural Killer cells – a type of white blood cell – are a major component of the human body’s innate, quick-response immune system, providing a fast frontline defence against tumours, viruses and bacterial infections.

The gene E4bp4 is the ‘master gene’ for NK cell production, which means it is the primary driver that causes blood stem cells in the bone marrow to differentiate into NK cells.

Led by Dr Hugh Brady, the researchers are hoping to progress with a drug treatment for cancer patients which reacts with the protein expressed by their E4bp4 gene, causing their bodies to produce a higher number of NK cells than normal, to increase the chances of successfully destroying tumours.

“If increased numbers of the patient’s own blood stem cells could be coerced into differentiating into NK cells, via drug treatment, we would be able to bolster the body’s cancer-fighting force, without having to deal with the problems of donor incompatibility,” Nature quoted Brady as saying.

The researchers proved the pivotal role E4bp4 plays in NK production when they knocked the gene out in a mouse model.

Without E4bp4 the mouse produced no NK cells whatsoever but other types of blood cell were unaffected.

“Now finally, with our discovery of the NK cell master gene and subsequent creation of our mouse model, we will be able to find out if the progression of these diseases is impeded or aided by the removal of NK cells from the equation. This will solve the often-debated question of whether NK cells are always the ‘good guys’, or if in certain circumstances they cause more harm than good,” said Brady.

The study has been published in Nature Immunology. (ANI)

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Turning off oncogene may inhibit lung cancer stem cells’ growth

September 10, 2009 By admin Leave a Comment

Washington, Sep 9 (ANI): A lung cancer oncogene, called PKCiota, is necessary for the proliferation of lung cancer stem cells, and turning it off could act as a key for the treatment of this deadly disease, according to scientists at the Mayo Clinic campus in Florida.

These stem cells are rare and powerful master cells that manufacture the other cells that make up lung tumours, and are resistant to chemotherapy treatment.

The study also shows that an agent, aurothiomalate, being tested at Mayo Clinic in a phase I clinical trial substantially inhibits growth of these cancer stem cells.

“Our data indicate that PKCiota is required for the earliest steps in the development of lung cancer, which is the expansion of tumor-initiating cells or cancer stem cells,” said the study’s senior author, Dr. Alan Fields.

“Lung cancer stem cells appear to be the major drivers in many common lung cancers, and in order for a therapeutic treatment to be effective, it has to disrupt these cancer stem cells. We show that aurothiomalate, the agent now being tested in lung cancer patients, can, in fact, target these cells,” he added.

While aurothiomalate was once used to treat rheumatoid arthritis, the researchers have now discovered that it can also target PKCiota.

Currently, the agent is being tested in patients at Mayo Clinic’s sites in Minnesota and Arizona and, based on this phase I trial, a phase II human clinical trial is planned to combine aurothiomalate with agents targeted at other molecules involved in cancer growth.

“We had previously shown that PKCiota is required to maintain tumor growth, but what this study sought to determine is whether PKCiota is involved in the initial steps of lung cancer development,” said Fields.

Fields said that, in mice, an oncogene known as Kras is thought to transform normal lung stem cells into cancer stem cells, thereby initiating lung cancer.

In the present study, the researchers established a strain of mice in which Kras can be activated at the same time that the PKCiota gene is inactivated.

They found that when the PKCiota gene is inactivated, Kras was unable to cause errant growth and expansion of lung stem cells in mice, the process that initiates tumour formation.

“What this told us is that Kras requires PKCiota to transform the lung stem cells and make them proliferate. In other words, PKCiota is downstream from Kras, and is necessary for Kras to initiate lung tumor formation,” said Fields.

After discovering that aurothiomalate disables PKCiota, the researchers tested whether this agent is effective against lung cancer that develops due to Kras mutation.

“The drug showed potent inhibitory effects on the Kras-dependent proliferation of lung cancer stem cells both in cell culture and in animals,” said Fields.

“That further suggests that a drug like aurothiomalate could have an effect on tumors that are dependent on either Kras or PKCiota for growth and survival, and that is potentially a lot of cancers.

Aurothiomalate appears to be one of the few drugs available that can effectively target these critical cancer stem cells. In the clinic, however, it is likely that aurothiomalate will be most effective when combined with other agents designed to target other tumor survival pathways,” he added.

The study has been published in Cancer Research. (ANI)

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New stem cell op may prevent thousands from having hip replacements

September 1, 2009 By admin Leave a Comment

London, August 31 (ANI): British surgeons at the Spire Hospital in Southampton are using a novel technique that uses stem cells to repair damaged bones.

Media reports on this procedure suggest that it may prevent thousands of people from needing to have an artificial hip fitted.

Mark Venables, 39, is one patient on whom doctors at the Spire Hospital conducted one of their first operations.

He suffers from a condition where bone in his hip died, weakening his joint and causing pain on movement.

The surgeons at the hospital used his own stem cells to rejuvenate the affected bone.

“I just want to get back to an active life,” Sky News quoted Venables as saying before the operation.

For the operation, the surgeons first purified stem cells from bone marrow that they had extracted from Venables’ pelvis.

The doctors then mixed them with cleaned, ground-up bone from another patient, who had had their own hip replaced.

After removing the dead tissue from the ball of his hip, the doctors filled the cavity with the mixture of stem cells and donated bone.

Surgeon Doug Dunlop said that the bone would have collapsed without the stem cell treatment, and that Venables would have then needed an artificial hip joint.

“If this new procedure works, he won’t need a hip replacement. It will fix his hip for life,” said Dunlop.

To date, six patients have been operated using the new procedure, and only one surgery has failed.

Professor Richard Oreffo, of Southampton University, is now hoping to improve the technique further by replacing the donated bone with an artificial material containing chemicals that help the stem cells grow.(ANI)

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Novel method to make safer human stem cells uses just one gene

August 29, 2009 By admin Leave a Comment

London, Aug 29 (ANI): Inching closer to curing diseases like Parkinson’s using cells generated from a patient’s own body, researchers have successfully reprogrammed human nerve cells back to an embryo-like state by using just a single gene.

It is known that embryonic stem cells are pluripotent – they can develop into any of the body’s cell types.

But such cells are not available in large numbers, as they can only be harvested from a donated egg or embryo, and, for ethical reasons, most countries have laws restricting their use.

In 2006, Shinya Yamanaka and his colleagues at Kyoto University in Japan successfully made mouse cells pluripotent by reprogramming skin cells into a state like embryo cells.

They did so by using retroviruses to insert four genes – known as “factors” – into the cells’ DNA.

They repeated the trick a year later with human cells.

However, using genes and retroviruses in this way increases the risk of the cell becoming cancerous, not just because tinkering with DNA has that effect, but also because two of the four factors are known to cause cancer.

In a bid to make these promising cells in a safe way, Hans Scholer’s team at the Max Planck Institute for Molecular Biomedicine in Münster, Germany, has been working to achieve pluripotency using fewer factors.

Last year, they did this with the two factors that do not cause cancer, and now they have simplified the recipe further, doing it with just one.

“Remarkably, it turns out that three of these four essential factors are already expressed in human neural stem cells – although not in skin cells – so we only needed to add one factor, OCT4,” New Scientist quoted Boris Greber, a member of the team, as saying.

He said that the cells from neural tissue are much easier to reprogram than skin cells, and are less prone to mutations.

It is much harder to get a sample of neural stem cells than skin cells, as it can be done via extracting the cells from the dental pulp of teeth, said Greber.

Inserting even one gene into the chromosome of a cell still permanently modifies its DNA, which is why the new method will remain a lab tool instead of being allowed in the clinic.

However, the researchers are hoping that it will help them improve methods for producing embryonic stem cells.

“Ideally, we will be able to find a chemical that does the same job of expressing the factor without the need for a gene,” said Greber.

Earlier this year, researchers in California managed just that when they reprogrammed mouse fibroblasts using a cocktail of proteins.

That technique did not involve inserting genes, and, thus, shouldn’t raise the cancer risk. But that was far less efficient.

“Without stable intervention using viruses, the frequency of reprogramming goes down and you have to wait a long time. We don’t have the perfect method yet,” said Greber.

The study has been published in the journal Nature. (ANI)

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Artificial red blood cells a step closer

August 25, 2009 By admin Leave a Comment

Melbourne, Aug 24 (ANI): A team of Australian scientists has genetically modified human embryonic stem cells to glow red when they develop into premature red blood cells.

The breakthrough is seen as the next step in producing artificial blood.

Dr Andrew Elefanty at Monash University in Melbourne and his colleagues inserted specific genes that code for colour, into the DNA of a manufactured stem cell line.

Stem cells are the template from which all cell types in the body form.

He says the coloured genes, known as ‘reporters’, highlight the emergence of certain cell types.

“What we’ve said to the stem cells is when you’re going to turn on the gene for globin we want you to also turn on a red light,” ABC Science quoted Elefanty as saying.

He says fluorescing cells are a useful tool to help work out the best way to engineer specific cells.

“We learn what the right growth enhancing substances are that the body normally uses and we put those into the laboratory,” he said.

Elefanty says fluorescing cells also allows scientists to monitor the cells when they’ve been injected into animals.

“Sometimes it’s not that easy to tell the difference between the ones you put in and the ones that were already there,” he said.

The researchers are hoping the development of glowing stem cell lines will help them work out how to develop mature red blood cells faster.

However, Elefanty says they are still a way off producing artificial blood that could be used in human blood transfusions.

He and his colleagues are working with Queensland researchers to develop ways to mature the cells, but there are still many issues to resolve.

“We’ve got to make sure the cells are safe, that they don’t keep growing and form tumours and that the immune system doesn’t reject them,” he said.

The research has been published in today’s edition of Nature Methods. (ANI)

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MRI methods can show bone marrow stem cells’ viability as brain-repairing therapy

August 20, 2009 By admin Leave a Comment

Washington, August 20 (ANI): Researchers at Tel Aviv University have offered new hope for people with incurable neurodegenerative diseases like Huntington’s, Alzheimer’s, and Parkinson’s by showing that the viability of stem cells created from a patient’s own bone marrow can be determined using MRI tracking methods.

Dr. Yoram Cohen, of TAU’s School of Chemistry, claims that he has been able to track the progress of the innovative cells called mesenchymal stem cells within the brain.

He says that initial studies indicate that it is possible to identify unhealthy or damaged tissues, migrate to them, and potentially repair or halt cell degeneration.

“By monitoring the motion of these cells, you get information about how viable they are, and how they can benefit the tissue. We have been able to prove that these stem cells travel within the brain, and only travel where they are needed. They read the chemical signalling of the tissue, which indicate areas of stress. And then they go and try to repair the situation,” he says.

During the study, Dr. Cohen and his colleagues tracked the activity of the live cells within the brain using the in-vivo MRI at the Strauss Centre for Computational Neuro-Imaging, with a view to establishing their viability as a therapy for neurodegenerative disease.

The researchers used magnetic iron oxide nanoparticles to label the stem cells, so that they could be identified as clear black dots on an MRI picture after being injected into the brain.

The stem cells were then injected into the brain of an animal that had an experimental model of Huntington’s disease, which suffered from a similar neuropathology as the one seen in human patients.

On MRI, it was possible to watch the stem cells migrating towards the diseased area of the brain.

“Cells that go toward a certain position that needs to be rescued are the best indirect proof that they are live and viable. If they can migrate towards the target, they are alive and can read chemical signalling,” says Dr. Cohen.

He believes that the benefits of using differentiated mesenchymal cells (MSC) may be numerous.

“Bone marrow-derived MSCs bypass ethical and production complications, and in the long run, the cells are less likely to be rejected because they come from the patients themselves. This means you don’t need immunosuppressant therapy,” he says.

Dr. Cohen has revealed that the next step in his research will be to develop a real-life therapy for those suffering from neurodegenerative diseases.

A researcher article on his study has been published in the journal Stem Cells. (ANI)

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Scientists discover deadly plant that eats rats

August 18, 2009 By admin Leave a Comment

London, August 18 (ANI): British scientists have discovered a deadly plant that eats rats, and is believed to be the largest meat-eating shrub.

According to a report in The Sun, the giant pitcher plant lures rodents into its slipper-shaped mouth and dissolves them with acid-like enzymes.

Scientists, led by botanists Stewart McPherson and Alastair Robinson, tracked it down on Mount Victoria in the Philippines after hearing that missionaries had seen “whole rats” being eaten.

“The plant produces spectacular traps which catch not only insects, but also rodents. It is remarkable that it remained undiscovered until the 21st century,” said McPherson, of Poole, Dorset.

The research team named the incredibly rare species after legendary wildlife broadcaster Sir David Attenborough.

“My team and I named it in honour of Sir David whose work has inspired generations toward a better understanding of the beauty and diversity of the natural world,” said McPherson.

“I was contacted by the team shortly after the discovery and they asked if they could name it after me. I was delighted and told them, ‘Thank you very much’,” said Sir David.

“I’m absolutely flattered. This is a remarkable species the largest of its kind. I’m told it can catch rats then eat them with its digestive enzymes. It’s certainly capable of that,” he added.

The plant, now dubbed Nepenthes attenboroughii, is green and red and can grow a stem more than 4ft long. It is found only in the scrub high on the windswept slopes of Mount Victoria.

McPherson and former Cambridge University botanist Robinson made their discovery during an expedition in 2007.

But, they have only just described the killer shrub in a journal after a three-year study of all 120 species of pitcher plant. (ANI)

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Scientists create artificial sperm cells from human embryonic stem cells

July 8, 2009 By admin Leave a Comment

London, July 8 (ANI): Scientists have achieved a major breakthrough in making sperm-like cells from human embryonic stem cells.

Karim Nayernia, of the University of Newcastle Upon Tyne in the UK, has revealed that these cells can swim like sperm do.

He says that his team used the same technique to create sperm-like cells from human embryonic stem cells that he had used in 2006 to produced sperm from mouse embryonic stem cells.

The team labelled embryonic stem cells with a fluorescent marker attached to a particular gene that is expressed during reproductive-cell development, and cultured the cells in a medium that encourages differentiation into sperm cells.

The researchers observed that about three per cent of the resulting cells contained enough DNA for only one set of chromosomes, suggesting that meiosis had occurred.

Some of these cells also formed tails and were motile, they said.

Nayernia and his colleagues have yet to analyse methylation patterns in their sperm-like cells, or conduct a detailed study of the cells’ morphology.

While there work has been hailed by other scientists, the sperm-like cells created by the researchers will still require much more characterization before they can be used as an experimental model for the study of inherited diseases and infertility.

Another hurdle is that, in several countries, it may actually be illegal even if these cells were properly characterised.

Nayernia admits it, but still insists that his team’s work was a “proof-of-principle experiment”.

“We don’t claim that it is fully normal sperm, but they do have some of the right characteristics,” Nature magazine quoted him as saying.

Meanwhile, he and his colleagues have also launched a project to produce sperm cells from induced pluripotent stem cells, which can be generated from adult cells.

The researchers believe that such cells would make it easier to derive sperm cells from many individuals.

“Then we can, for example, see whether environmental factors or genetic factors are affecting fertility, and which step of sperm production has been affected by those factors,” he says. (ANI)

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Indian-origin scientist finds genetic switch that may help treat vascular diseases

July 6, 2009 By admin Leave a Comment

London, July 6 (ANI): Taking a big leap towards finding a treatment of vascular diseases, a team led by an Indian-origin scientist at the Gladstone Institute of Cardiovascular Disease (GICD) has discovered a key switch that makes stem cells turn into the type of muscle cells that reside in the wall of blood vessels.

Dr. Deepak Srivastava’s study claimed that the same switch could be used in the future to limit growth of vascular muscle cells that cause narrowing of arteries leading to heart attacks and strokes, limit formation of blood vessels that feed cancers, or make new blood vessels for organs that are not getting enough blood flow.

It was found that a tiny RNA molecule, called microRNA-145 (miR-145), not only had all the information necessary to turn a stem cell into a vascular smooth muscle cell (VSMC), but could also affect VSMCs in the adult artery.

VSMCs possess the unique property of dividing on their own when an artery is injured or during atherosclerosis, ultimately causing narrowing of the vessel leading to occlusion.

The researchers found that miR-145 and its sister microRNA, miR-143, work together to stop the pathologic division of VSMCs.

But in the setting of vessel disease, their activity was turned down, which made the VSMCs to divide and clog up the artery.

MicroRNAs are small RNA molecules that do not make protein, but instead affect that amount of protein synthesized by the cell from their target mRNAs-the blueprints for translating the genetic code into proteins.

The researchers found that miR-145 and miR-143 together controlled the synthesis of a network of “master regulators” that control VSMCs, and thereby were able to function as a central “switch” for the behaviour of these important cells.

“The ability of miR-145 to efficiently direct the cell fate of vascular smooth muscle cells from stem cells represents the power of these tiny microRNAs to exert major effects on cells. We hope that we can use this knowledge to control when the body makes or does not make new blood vessels,” Nature magazine quoted Srivastava as saying.

He added: “Our findings in this study offer insights into regulatory mechanisms that govern the differentiation and proliferation of smooth muscle. They have fundamental implications for the treatment of vessel diseases like atherosclerosis and also may be important for cancer.”

The study has been published in the current issue of the journal Nature. (ANI)

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Novel targeted therapy shows promise to eliminate leukaemia stem cells

July 3, 2009 By admin Leave a Comment

Washington, July 3 (ANI): A piece of research has shown that it is possible to eliminate stem cells related to human acute myeloid leukemia (AML), a notoriously treatment-resistant blood cancer, using a new targeted therapy.

Associate Professor Richard Lock, from the Children’s Cancer Institute Australia and the University of New South Wales, has revealed that the new therapeutic approach has been found to selectively attack human cancer cells grown in the lab as well as in animal models of leukaemia.

AML is a cancer of the white blood cells that has an extremely poor prognosis and does not respond well to conventional chemotherapy.

“The cellular and molecular basis for this dismal picture is unclear. However, previous research has suggested that leukaemia stem cells (LSCs) may lie at the heart of post-treatment relapse and chemoresistance,” says Lock.

LSCs are cells that can initiate AML and are critical for its long-term growth.

Lock and his colleagues exploited the fact that the molecule CD123 is expressed at very high levels on LSCs but not on normal blood cells.

The researchers created a therapeutic antibody that recognized and bound to CD123, hoping that the antibody would selectively interfere with AML-LSC survival.

When AML-LSCs from human patients were transplanted into mice treated with the antibody, called 7G3, cytokine signalling in the tumour cells was blocked.

The research team also observed that 7G3 impaired migration of the AML-LSCs to bone marrow, and activated the innate immune system of the host mouse to destroy the AML-LSCs.

They say that, overall, treatment with 7G3 substantially improved mouse survival when compared with control groups.

Lock and his colleagues are currently using a CD123-targeting antibody in phase 1 clinical trials of advanced AML. They say that there are no signs of treatment-related toxicity.

These results hold substantial promise for future cancer therapeutics.

“The recent characterization of defined populations of cancer stem cells in a range of human malignancies, as well as their relative resistance to conventional chemotherapy and radiotherapy, supports the broad applicability of our approach and provides rationale for the progression of AML-LSC-targeted therapeutics from preclinical evaluation to clinical trials,” concludes Associate Professor Lock.

A research article on the study has been published in the journal Cell Stem Cell. (ANI)

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Bone marrow extract therapy after heart attack improves cardiac function

June 30, 2009 By admin Leave a Comment

Washington, June 30 (ANI): A new study has found that an extract derived from bone marrow cells is as effective as therapy using bone marrow stem cells for improving cardiac function after a heart attack.

The study was conducted in mice using a novel stem cell delivery method developed by researchers to show that the extract from bone marrow cells is as beneficial to cardiac function as are intact, whole cells.

Both the cell and cell extract therapies resulted in the presence of more blood vessels and less cardiac cell death, or apoptosis, than no therapy.

The study also showed that heart function benefitted despite the finding that few of the injected cells remained in the heart at one month after therapy.

“Peer-reviewed medical literature is controversial as to whether bone marrow cells differentiate into cardiomyocytes, or cardiac muscle cells, but there is general agreement that stem cell therapy with these cells results in some level of functional improvement after a heart attack. The exact mechanism for this is not yet clear,” said Yerem Yeghiazarians, MD, study author, cardiologist and director of UCSF’s Translational Cardiac Stem Cell Development Program.

“Our results confirm that whole cells are not necessarily required in order to see the beneficial effects of bone marrow cell therapy,” Yeghiazarians added.

Researchers are investigating these new therapies to improve cardiac function after heart attack in an effort to prevent heart failure.

“Current therapies improve symptoms but do not replace scar tissue. Our hope is to use stem cells to decrease the scar, minimize the loss of cardiac muscle and maintain or even improve the cardiac function after a heart attack,” Yeghiazarians said.

The researchers are conducting further studies to evaluate bone marrow cell and extract therapies in order to identify the proteins and factors within the extract and gain insight into the possible mechanisms of cardiac functional improvement.

The findings were published online and in the July 2009 issue of the Journal of Molecular Therapy. (ANI)

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Non-invasive stem cell procedure shows promise to repair heart tissue

May 29, 2009 By admin Leave a Comment

Washington, May 29 (ANI): For the first time, researchers at the University at Buffalo have shown that it is possible to repair cardiac tissue and, in turn, reverse heart failure by injecting adult bone marrow stem cells into skeletal muscle.

The researchers used an animal model to demonstrate that the non-invasive procedure could increase myocytes, or heart cells, by two-fold and reduce cardiac tissue injury by 60 percent.

In addition, the therapy improved function of the left ventricle-the primary pumping chamber of the heart-by 40 percent.

It even reduced fibrosis-the hardening of the heart lining that impairs its ability to contract-by up to 50 percent.

“This work demonstrates a novel non-invasive mesenchymal stem cell (MSC) therapeutic regimen for heart failure based on an intramuscular delivery route,” said Dr. Techung Lee, UB associate professor of biochemistry and senior author on the paper.

Mesenchymal stem cells are found in the bone marrow, and can differentiate into a variety of cell types.

Lee said: “Injecting MSCs or factors released by MSCs improved ventricular function, promoted myocardial regeneration, lessened apoptosis (cell death) and fibrotic remodeling, recruited bone marrow progenitor cells and induced myocardial expression of multiple growth factor genes.

“These findings highlight the critical ‘cross-talks’ between the injected MSCs and host tissues, culminating in effective cardiac repair for the failing heart.

“An important feature of MSCs is their ability to produce a plethora of tissue healing effects, known as “tropic factors,” which can be harnessed for stem cell therapy for heart failure.

The multiple trophic factors produced by MSCs have already been shown to be capable of reducing tissue injury, inhibiting fibrosis, promoting angiogenesis, stimulating recruitment and proliferation of tissue stem cells, and reducing inflammatory oxidative stress, a common cause of cardiovascular disease and heart failure.

Lee added: “Since skeletal muscle is the most abundant tissue in the body and can withstand repeated injection of large number of stem cells, we thought it would be a good method to deliver MSCs. We hypothesized that MSCs, via secretion of these functionally synergistic trophic factors, would be able to rescue the failing heart even when delivered away from the myocardium.

“This study proves our hypothesis. We’ve demonstrated that injecting MSCs, or trophic factors released by MSCs, into skeletal muscle improved ventricular function, promoted regeneration of heart tissue, decreased cell death and improved other factors that cause heart failure.

“This non-invasive stem cell administration regimen, if validated clinically, is expected to facilitate future stem cell therapy for heart failure.”

The development has been reported in a paper appearing online in the Articles-in-Press section of the American Journal of Physiology-Heart Circulation Physiology. (ANI)

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Gene therapy ‘helps minimize risk linked to stem cell transplantation’

May 22, 2009 By admin Leave a Comment

Washington, May 22 (ANI): Researchers from NewYork-Presbyterian Hospital/Weill Cornell Medical Centre suggest that genetically modifying stem cells prior to transplantation can help minimize the risk associated with the therapy.

Stem cells intended to treat or cure a disease can end up wreaking havoc simply because they are no longer under the control of the clinician.

“Stem cell therapy offers enormous potential to treat and even cure serious diseases. But wayward stem cells can turn into a runaway train without a conductor,” said senior author Dr. Ronald G. Crystal, chief of the Division of Pulmonary and Critical Care Medicine at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

“This is an issue that can be dealt with and we have the technology to do that in the form of gene therapy,” he added.

Researchers said that one of the biggest potential problems with stem cell therapy is the development of tumors.

Also stem cells directed to become beating heart cells might mistakenly end up in the brain. Or insulin-producing beta cells which can’t stop means the body can no longer regulate insulin levels.

The best way to avoid the problems is genetic modification of the stem cells prior to actually transplanting them, Dr. Crystal said.

“Almost all therapeutics we use have a half life. They only last a certain amount of time,” he said.

“Stem cells are the opposite. Once the future stem cell therapist does the therapy, stem cells have the innate potential to produce more cells,” he added.

The study appears in the journal Cell Stem Cell. (ANI)

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Personalised cancer treatment comes closer to reality

May 18, 2009 By admin Leave a Comment

London, May 18 (ANI): Researchers at the University of California, San Diego School of Medicine have announced the development of an efficient system for delivering siRNA into primary cells, which may one day lead to personalized cancer treatment.

“RNAi has an unbelievable potential to manage cancer and treat it,” Nature magazine quoted Dr. Steven Dowdy, Howard Hughes Medical Institute Investigator and professor of cellular and molecular medicine at UC San Diego School of Medicine, as saying .

“While there’s still a long way to go, we have successfully developed a technology that allows for siRNA drug delivery into the entire population of cells, both primary and tumor-causing, without being toxic to the cells,” he added.

The researcher has revealed that his study focussed on the potential for a small section of protein called peptide transduction domain (PTD), which has the ability to permeate cell membranes, as a delivery mechanism for getting siRNAs into cancer cells.

In their previous work, he and his colleagues had generated over 50 “fusion proteins” using PTDs linked to tumour-suppressor proteins.

“Simply adding the siRNAs to a PTD didn’t work, because siRNAs are highly negatively charged, while PTDs are positively charged, which results in aggregation with no cellular delivery,” Dowdy said.

He said that his team solved the problem by making a PTD fusion protein with a double-stranded RNA-binding domain, termed PTD-DRBD, which masks the siRNA’s negative charge.

According to him, this allows the resultant fusion protein to enter the cell and deliver the siRNA into the cytoplasm, where it specifically targets mRNAs from cancer-promoting genes and silences them.

With a view to testing the PTD-DRBD fusion protein’s ability to deliver siRNA, the researchers generated a human lung cancer reporter cell line. They used green and fluorescent protein and analysed the cells using flow cytometry analysis.

Their efforts enabled them to determine the magnitude of RNA inhibitory response and the percentage of cells undergoing this response.

They found that the entire cellular population underwent a maximum RNAi response. Similar results were obtained in primary cells and cancer cell lines.

“We were subsequently able to introduce gene silencing proteins into a large percentage of various cell types, including T cells, endothelial cells and human embryonic stem cells. Importantly, we observed no toxicity to the cells or innate immune responses, and a minimal number of transcriptional off-target changes,” said Dowdy.

The researchers are of the opinion that the RNAi methods can be continually tweaked to combat new mutations, a way to overcome a major problem associated with current cancer therapies.

“Such therapies can’t be used a second time if a cancer tumor returns, because the tumor has mutated the target gene to avoid the drug binding. But since the synthetic siRNA is designed to bind to a single mutation and only that mutation on the genome, it can be easily and rapidly changed while maintaining the delivery system – the PTD-DRBD fusion protein,” said Dowdy. Cancer is a complex, genetic disease that is different in every patient. This is still in early stages, but I believe the siRNA-induced RNAi approach to personalized cancer treatment is the only thing on the table,” Dowdy added.

The study has been published in the advance on-line edition of the journal Nature Biotechnology. (ANI)

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Embryo’s heartbeat triggers blood stem cell formation

May 14, 2009 By admin Leave a Comment

Washington, May 14 (ANI): In a breakthrough study, researchers have found that heartbeat and blood circulation play key role in the formation of blood cells in embryos.

The finding might provide an answer to why embryonic heart begins beating so early even before the tissues actually need to be infused with blood.

Researchers hope that clues about how blood forms could provide new strategies for treating blood diseases such as leukemia, immune deficiency and sickle cell anaemia.

During the study, Dr Leonard Zon, of the Division of Hematology/Oncology at Children’s and Director of its Stem Cell research program used zebrafish, whose transparent embryos allow direct observation of embryonic development.

They found that compounds that modulate blood flow had a potent impact on the expression of a master regulator of blood formation, known as Runx1.

The study, appearing in journal Cell, showed that nitric oxide, whose production is increased in the presence of blood flow, is the key biochemical regulator.

Increasing nitric oxide production restored blood stem cell production in the mutant fish embryos, while inhibiting nitric oxide production led to reduced stem cell number.

“Nitric oxide appears to be a critical signal to start the process of blood stem cell production,” said Zon.

“This finding connects the change in blood flow with the production of new blood cells,” he added.

Another study published in Nature, showed that blood flow also triggers blood-forming or hematopoietic stem cell production in mouse embryos.

The researchers showed that shear stress – the frictional force of fluid flow on the surface of cells lining the embryonic aorta – increases the expression of master regulators of blood formation, including Runx1, and of genetic markers found in blood stem cells.

It also increased formation of colonies of progenitor cells that give rise to specific lineages of blood cells.

This showed that biomechanical forces promote blood formation.

“In learning how the heartbeat stimulates blood formation in embryos, we’ve taken a leap forward in understanding how to direct blood formation from embryonic stem cells in the petri dish,” said lead researcher Dr George Q.

Daley, director of the Stem Cell Transplantation Program at Children’s Hospital Boston. (ANI)

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New way to reduce tumour-risk factor in stem cell therapy unveiled

May 7, 2009 By admin Leave a Comment

Washington, May 7 (ANI): Paving the way for advancement in the field of stem cell therapy, scientists have discovered a method to potentially eliminate the tumour-risk factor in utilizing human embryonic stem cells.

Human embryonic stem cells are theoretically capable of differentiation to all cells of the mature human body, and are hence defined as “pluripotent”.

The above capability, along with the ability to remain undifferentiated indefinitely in culture, make regenerative medicine using human embryonic stem cells a potential tool for the treatment of various diseases, including diabetes, Parkinson’s disease and heart failure.

However, the biggest hurdle in using stem cells is their tendency to grow into a specific kind of tumour, called teratoma, when they are implanted in laboratory experiments into mice.

And scientists have thought that the tumorigenic feature will be manifested upon transplantation to human patients as well.

Thus the development of tumours from embryonic stem cells is especially puzzling, keeping in mind that these cells start out as completely normal cells.

So, researchers at the Stem Cell Unit in the Department of Genetics at the Silberman Institute of Life Sciences at the Hebrew University analysed the genetic basis of tumour formation from human embryonic stem cells, and identified a key gene that is involved in this unique tumorigenicity.

The gene called survivin is expressed in most cancers and in early stage embryos, but it is almost completely absent from mature normal tissues.

The gene is especially highly expressed in undifferentiated human embryonic stem cells and in their derived tumours.

The researchers could neutralise the activity of survivin in the undifferentiated cells as well as in the tumours, and thus managed to initiate programmed cell death (apoptosis) in those cells.

The inhibition of this gene just before or after transplantation of the cells could minimize the chances of tumour formation.

But the researchers have warned that a combination of strategies may be needed to address the major safety concerns regarding tumour formation by human embryonic stem cells. (ANI)

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Novel genetic regulator involved in head, throat cancers discovered

May 2, 2009 By admin Leave a Comment

Washington, Apr 29 (ANI): In a major scientific advancement, pharmacy researchers at Oregon State University have discovered a genetic regulator, called CTIP2, which is expressed at higher levels in the most aggressive types of head and neck cancers.

The study might help in the identification of these cancers earlier or even offer a new therapy at some point in the future.

In a recent research, the “transcriptional regulator” CTIP2 was demonstrated to be a master regulator that has important roles in many biological functions, ranging from the proper development of enamel on teeth to skin formation and the possible treatment of eczema or psoriasis.

But, in the latest study, scientists found for the first time that levels of CTIP2 were more than five times higher in the “poorly differentiated” tumour cells that caused the most deadly types of squamous cell carcinomas in the larynx, throat, tongue and other parts of the head.

The researchers even found a high correlation between greater CTIP2 expression and the aggressive nature of the cancer.

They said that head and neck squamous cell cancers are the sixth most common cancers in the world, and a significant cause of mortality. They have been linked to such things as tobacco use and alcohol consumption.

“Serious head and throat cancer is pretty common, and mortality rates from it haven’t improved much in 20 years, despite new types of treatments. With these new findings, we believe it should be possible to create an early screening and diagnostic tool to spot these cancers earlier, tell physicians which ones need the most aggressive treatments and which are most apt to recur,” said Gitali Indra, an assistant professor in the OSU College of Pharmacy.

The scientists hope that the work could lead to new therapeutic approaches.

Also they said that this genetic regulator could be involved in both skin development and these types of cancer makes some sense, as both originate from epithelial cells.

The study speculated that CTIP2 could help regulate the growth of what is believed to be a cancer “stem” or “progenitor” cell, which has a greater potential to generate tumours through the stem cell processes of self-renewal and differentiation into multiple cell types.

Therefore, targeting cancer stem cells holds promise for improvement of survival and quality of life of cancer patients.

The study is published in PLoS ONE a professional journal. (ANI)

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