DAVID GRANOVSKY

Archive for November, 2012|Monthly archive page

RESEARCHERS DISCOVER KEY TO STEM CELL THERAPY FOR MS PATIENTS

In STEM CELLS IN THE NEWS on November 30, 2012 at 9:00 am

 clinical trial capsules

We know stem cells work on MS, we just hadn’t figured out exactly how yet…and now we have!

– DG

CLEVELAND, Ohio — One of the most promising and exciting treatment avenues for multiple sclerosis is the use of a patient’s own stem cells to try to stop — or even repair — some of the disease’s brain tissue damage.

But injecting a patient with a dose of his or her own bone-marrow stem cells was actually a pretty crude method of treating the disease, because no one was quite sure how or why it worked. Last year, doctors at the Cleveland Clinic, University Hospitals Seidman Cancer Center and Case Western Reserve University began trying this for MS patients in a Phase 1 clinical trial after positive results were seen in mice.

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheaths that surround and protect nerve cells. When myelin is damaged, the nerve cells are exposed and unable to do their job, which is sending signals to the brain and back. This results in the loss of motor skills, coordination and cognitive abilities.

Like many other researchers using stem cells, the local group didn’t know exactly how their treatment worked, but they knew that when they gave these human mesenchymal stem cells, or MSCs, to mice with a mouse version of the disease, the mice got better.

Figuring out why the mice improved could help researchers see if the MSC injection will work well in a particular patient before the patient is injected, and possibly augment or improve the treatment as well.

In May, the research group at CWRU, headed up by neurosciences professor Robert Miller, discovered exactly what it is in the stem-cell soup that has a healing effect: a large molecule called hepatocyte growth factor, or HGF. The team published their results in Nature Neuroscience.

Miller’s group knew that it could be the stem cells themselves, by coming in physical contact with the myelin damage, that were having a healing effect. Or it could be something the stem cells secreted into the surrounding liquid culture, or media, they were grown in, that was key. HGF is secreted by the stem cells, Miller said.

The team identified the HGF by first injecting only the liquid the stem cells were grown in, but not the stem cells themselves, into the mice they were studying. The mice got better, so the team knew whatever was helping was in the media.

Next, they isolated the small, medium and large molecules from the media and tried each size on the mice. Only the large-molecule treatment had the healing effect, meaning that whatever was helping was somewhere in that mix, Miller said.

“The molecule that jumped out at us was HGF,” he said, because it is the right size, is made by MSCs, and in a couple of studies had been shown to be involved in myelin repair.

So the scientists took a purified sample of HGF and injected it into the sick mice. They got better. When they blocked the receptor for HGF in the mice, they stayed sick. It was pretty compelling evidence that they’d found what they’d been looking for, Miller said.

“We went on to show that HGF, like the MSCs, is regulating both the immune response, and it is independently promoting myelin repair in the brain,” he said.

MSCs, taken from the bone marrow, are currently being tested in more than 150 clinical trials in the United States and around the world to treat conditions such as osteoarthritis, diabetes, emphysema and stroke.

The local Phase 1 trial has enrolled 16 of 24 total patients, and eight of them have completed the trial protocol, said Dr. Jeffrey Cohen, Cleveland Clinic neurologist and lead investigator of the trial.

So far, the treatment seems to be working, Cohen said.

“It’s a little early to be saying it, but things have looked encouraging.”

And there have been no safety concerns and almost no side effects. There has also been no activation — an aggravation or return of symptoms — of this relapsing disease in the patients involved, which has happened unexpectedly with other types of MS treatments.

Miller’s discovery won’t change the course of the trial currently under way at the Clinic and UH, but it may change the future of MSC treatment.

While they don’t know yet what the outcome of that trial will be, it’s possible that if a patient doesn’t respond to the treatment, it could mean that his stem cells aren’t producing enough HGF to be effective at healing, Miller said. Miller will be studying MSC samples from all the patients in the trial to find out if those who are better at producing HGF fare better.

He’ll also be trying to see if they can predict how well a patient will do based on his HGF levels in the MSC sample.

“Finally, though we’re a long way from this, maybe we could augment the expression of HGF in patients whose stem cells aren’t that effective to enhance their effectiveness,” he said.

But why not just inject the HGF alone? Miller said there are two reasons. First, the receptor for HGF in the cells, called c-MET, has been implicated in liver and breast cancer. Injecting HGF by itself into the body may stimulate the c-MET pathway, he said, and the research team is not willing to risk that.

“The stem cells have the advantage that they tend to home to the area of insult, so they don’t stick around in other parts of the body,” he said. “They target the treatment where it’s needed.”

Miller said his group is experimenting with a way of delivering HGF directly into the area of injury in the brain to minimize its contact with the rest of the body. HGF and c-MET are not associated with brain tumors.

They are also trying to test small fragments of the growth factor as a treatment, to see if they can eliminate some of the cancer concerns.

Cohen’s group hopes to have results from the Phase 1 trial available in the spring and has already started planning a larger study based on those results.

http://www.cleveland.com/healthfit/index.ssf/2012/09/cleveland_researchers_find_key.html

INDIA TO START STEM CELL THERAPY TRIALS FOR SPINAL CORD INJURIES

In STEM CELLS IN THE NEWS on November 29, 2012 at 9:00 am

 A bone marrow harvest.

Ahead of a planned five-centre nationwide trial, the Indian Council of Medical Research (ICMR) has approved a special project at the AIIMS Trauma Centre in New Delhi where stem cell therapy will be conducted on complete paraplegics and quadriplegics to try and revive limb function.

A similar trial will be conducted at the Indian Spinal Injuries Centre (ISIC) in Vasant Kunj, south-west Delhi where 21 patients have already been registered. This project too has been approved by the ICMR. Senior ICMR scientists from the apex committee to monitor stem cell research said the five-centre trial will be coordinated from ISIC and is in the final stages of approval.  “This will be the first national ICMR trial of autologous bone marrow stem cell transplant on complete quadriplegics and paraplegics. We are finalizing the number of patients. The ISIC will be the coordinating centre. The next meeting has been scheduled for December 4,” a senior scientist said.

An autologous stem cell transplantation is a procedure in which stem cells are removed, stored and returned to the same person.  For its project, the AIIMS Trauma Centre has registered eight patients. They will be injected with stem cells from their own bone marrow to see if the damaged neurological function can be regenerated. Doctors have cautioned that earlier trials on incomplete quadriplegics and paraplegics have not suggested significant clinical improvement.

Dr. Deepak Aggarwal, associate professor of neurosurgery at the AIIMS Trauma Centre who is coordinating the study, said: “We have necessary clearances from our internal ethics committee and the national apex committee for stem cell research and therapy which has members from the ICMR and Department of Biotechnology.”

“We are trying to see if injecting patients of irreversible spinal cord injuries with stem cells from their own bone marrow, under autologous stem cell transplantation, can help regenerate neurological function,” he said.   According to Dr. Aggarwal, clinical evidence in previous international trials have not given “satisfactory results”. This is the first time that AIIMS is undertaking such a project.

At the ISIC, doctors have selected 21 complete paraplegics who are being injected with stem cells retrieved from their own bone marrow within 10-14 days of injury.  “We had done one project in 2009 to see the use of stem cell transplant in restoring limb function on spinal cord injuries, but we had only selected chronic patients where the time lapse after the injury was far more. We could not demonstrate any clinical improvement. One criticism was that the spinal cord loses its plasticity and ability to regenerate after such a long time,” Dr. H S Chhabra, medical director at ISIC, said.

In the 2009 study, where five patients were selected, the site of stem cells was the olfactory mucosa or the upper region of the nasal cavity. For the new trial at ISIC, stem cells are being retrieved from the bone marrow of patients.  At AIIMS, patients will be monitored for six months after one procedure. If there is no significant change, another procedure of extraction of stem cells and autologous transplantation will be repeated. There will be follow-ups for two years.

Of the eight patients shortlisted for the project at AIIMS, three are quadriplegics and have lost function in all four limbs. Patients were evaluated to ensure only those with “complete” loss of limb function were included, and all within six months of injury.

At ISIC, the 21 patients have been divided into three arms. The first group will be injected stem cells directly into the spinal cord, at the site of injury. For the second group, stem cells will be injected into the cerebrospinal fluid that surrounds the spinal cord.

The third arm, which will be the control arm, will not be injected with stem cells, but given other rehabilitative therapies. The functional outcome of all three groups will be compared at the end of two years.

http://www.indianexpress.com/news/two-delhi-centres-ready-to-try-stem-cell-therapy-on-paraplegics/1036299/

A DIFFERENT KIND OF STEM CELL

In SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on November 26, 2012 at 8:05 am

Human fibroblast

A research team at Georgetown Lombardi Comprehensive Cancer Center say the new and powerful cells they first created in the laboratory a year ago constitute a new stem-like state of adult epithelial cells. They say these cells have attributes that may make regenerative medicine truly possible.”  This advancement could potentially guide research into a new era of personalized medicine.

-DG

In the November 19 online early edition of the Proceedings of the National Academy of Sciences (PNAS), they report that these new stem-like cells do not express the same genes as embryonic stem cells and induced pluripotent stem cells (iPSCs) do. That explains why they don’t produce tumors when they grow in the laboratory, as the other stem cells do, and why they are stable, producing the kind of cells researchers want them to.  “These seem to be exactly the kind of cells that we need to make regenerative medicine a reality,” says the study’s senior investigator, Richard Schlegel, M.D., Ph.D., chairman of the department of pathology at Georgetown Lombardi, a part of Georgetown University Medical Center.

This study is a continuation of work that led to a breakthrough in December 2011 when Schlegel and his colleagues demonstrated that he and his team had designed a laboratory technique that keep both normal as well as cancer cells alive indefinitely — which previously had not been possible.  They had discovered that adding two different substances to these cells (a Rho kinase inhibitor and fibroblast feeder cells) pushes them to morph into stem-like cells that stay alive indefinitely. When the two substances are withdrawn from the cells, they revert back to the type of cell that they once were. They dubbed these cells conditionally reprogrammed cells (CRCs).

The advance was seen as an exciting demonstration of personalized cancer medicine. In fact, a case study authored by Schlegel and his team, reported in the September 27 issue of the New England Journal of Medicine (NEJM), demonstrated how CRCs derived from normal and tumor cells of a 24-year-old man with a rare type of lung tumor allowed physicians to identify an effective cancer therapy. These cells were used to screen potential treatments and in this way, the scientists were able to see which therapies were active against the tumor cells and less harmful to the normal cells.

“Our first clinical application utilizing this technique represents a powerful example of individualized medicine,” Schlegel said in September. But he cautioned, “It will take an army of researchers and solid science to figure out if this technique will be the advance we need to usher in a new era of personalized medicine.”

This study was designed to see how the CRCs compared to known properties of embryonic stem cells and iPSCs, which are adult cells that have been manipulated by addition of genes to make them capable of differentiating (morphing into new adult cell types).  Both embryonic stem cells and iPSCs have been investigated for use in regenerative medicine, but each can form tumors when injected into mice and “it is difficult to control what kind of cells these cells differentiate into,” Schlegel says.  “You may want them to be a lung cell, but they could form a skin cell instead.”

In contrast, cells derived from the lung will develop stem-like properties when the conditions are added, allowing expansion of the lung cell population. However, when the conditions are withdrawn, they will revert to differentiated lung cells, he says. Schlegel added that they do this rapidly — within three days of adding the inhibitor and feeder cells, they efficiently generated large numbers of stem-like cells. It is also completely reversible: when the conditions are taken away, the cells lose their stem-like properties and potentially can be safely implanted into tissue.

The researchers compared gene expression between the three cell types and found that while some of the same genes are expressed in all the cells, CRCs don’t over express the same critical genes that embryonic stem cells and iPSCs do. “Because they don’t express those genes, they don’t form tumors and they are lineage committed, unlike the other cells,” Schlegel says. “That shows us that CRCs are a different kind of stem-like cell.”  As part of the study, the research team showed that when cervical cells are conditioned and placed on a three-dimensional platform, they start to form cells that “look like the cervix,” Schlegel says. The same is true from cells in the trachea — on a 3-D platform, they begin to look like a trachea, he says.

If and when use of CRCs are perfected for the clinic — and that will take considerable work, Schlegel says — they potential could be used in a wide variety of novel ways.  “Perhaps they could be used more broadly for chemosensitivity, as we demonstrated in the NEJM study, for regenerative medicine to replace organ tissue that is damaged, for diabetes — we could remove remaining islet ells in the pancreas, expand them, and implant them back into the pancreas —and to treat the many storage diseases caused by lack of liver enzymes. In those cases, we can take liver cells out, expand them and insert normal genes in them, and put them back in patients,” Schlegel says.  “The potential of these cells are vast, and exciting research to help define their ability is ongoing,” he says.
The research described was funded by a grant to Schlegel from the National Institutes of Health (R01 CA106400) with additional support from an additional NIH grant (5 U42 RR006042). Georgetown University has filed a patent application on the technology described in this paper. Schlegel is an inventor for the patent application.

http://explore.georgetown.edu/news/?ID=67774&PageTemplateID=295

HEART REPAIR THROUGH STEM CELLS

In SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on November 25, 2012 at 9:20 am

Big Heart of Art - 1000 Visual Mashups

Just as in holistic medicine where like heals like, it appears the closer the stem cell source to the desired target tissue or organ, the better the result. The less manipulated the better.   Forcing cells to become something they should not would appear to constitute wasted efforts. Using available and similar cells which transform without significant intervention to treat patients supports the adage: “less is more.” this prompts the level of involvement from scientists in the natural healing process of the body and the question, “should we differentiate at all?” Work smarter, not harder.
– DG

Recently, I blogged on blood vessel-making stem cells located in the walls of blood vessels. New work on these cells from the University of Pittsburgh has shown that these CD146+ cells can also abate heart damage after a heart attack.

The ability of endothelial progenitor cells or EPCs to repair skeletal muscle is well established, but the ability of these cells to repair a damaged heart is unknown. Johnny Huard from the McGowan Institute for Regenerative Medicine at the University of Pittsburgh and his group investigated the therapeutic capabilities of human blood vessel-derived EPCs that had been isolated from skeletal muscle to treat heart disease in mice.

When mice that had been given infusions of EPCs after a heart attack were compared with mice that had received a placebo, the EPC transplanted mice definitely fared much better. Echocardiographic studies of the hearts showed that EPC transplantation reduced enlargement of the left ventricle (the main pumping chamber of the heart), and also significantly improved the ability of the heart to contract.

In addition to comparing the ability of EPCs to improve the function of the heart after a heart attack with placebos, they were also compared to stem cells known to make skeletal muscle. These stem cells are called “CD56+ myogenic progenitor cells,” which is a mouthful. CD56+ myogenic progenitor cells or CD56+ MPCs can form skeletal muscle; and infusions of them can improve the structure of the heart after a heart attack and prevent it from deteriorating. However, transplanted EPCs were superior to CD56+ MPCs in their ability to heal the heart after a heart attack.

The transplanted EPCs were able to substantially reduced scarring in the heart, and significantly reduced inflammation in the heart. In fact, then the culture medium in which EPCs were grown was injected into mouse hearts after a heart attack, this medium also suppressed inflammation in the heart.

When Huard and his co-workers examined the genes made in the EPCs, they found that these stem cells cranked out proteins known to decrease inflammation (IL-6, LIF, COX-2 and HMOX-1 for those who are interested), especially when the cells were grown under low oxygen conditions. This is significant because in the heart after a heart attack, blood vessels have died off and the supply of blood to the heart is compromised. The fact that these cells are able to do this under these harsh conditions shows that they make exactly the most desirable molecules under these conditions.

The biggest boon for these cells came from examinations of blood vessel formation in the heart. Blood vessel production in the EPC-transplanted hearts was significantly increased. The EPCs formed a host of new blood vessels and extending “microvascular structures” or smaller supporting blood vessels and larger capillary networks too.

Once again, when grown under oxygen poor conditions, the EPCs jacked up their expression of pro-blood vessel-making molecules (VEGF-A, PDGF-β, TGF-β1 and their receptors). When EPCs were labeled with a green-glowing protein, fluorescence tracking showed that they actually fused with heart cells, although it must be emphasized that this was a minor event.

These pre-clinical studies show remarkable improvements in the heart after a heart attack, and they apparently induce these improvements through several different mechanisms. They make new structures and they secrete useful molecules. These significantly successful results should provide the basis for clinical trials with these cells.

http://beyondthedish.wordpress.com/2012/11/22/human-blood-vessel-derived-stem-cells-repair-the-heart-after-a-heart-attack/

STEM CELLS PROTECT BRAIN AFTER TRAUMATIC BRAIN INJURY

In SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on November 25, 2012 at 8:49 am

B0001870 Compromised blood brain barrier

Researchers have found new evidence supporting the benefits of using Mesenchymal stem cells (MSCs) for treatment of traumatic brain injury.  MSCs have the ability to stop inflammation and unwanted immune responses, through the production of metalloproteinase-3, which is essential in the recovery of the Blood Brain Barrier (BBB).  This discovery can change the way doctors treat traumatic brain injury and can foster the creation of a new, non-evasive technique, which utilizes the patient’s stem cells. – DG

Mesenchymal stem cells MSCs are found in multiple tissues and locations throughout our bodies, and they have the ability to differentiate into bone, fat, cartilage, and smooth muscle. MSCs also have the ability to suppress unwanted immune responses and inflammation. Therefore, MSCs are prime candidates for regenerative medical treatments. 

MSCs have been used to experimentally treat traumatic brain injury for example, Galindo LT et al., Neurol Res Int 2011;2011:564089. One of the main concerns after traumatic brain injury is damage to the (blood brain barrier) BBB. BBB damage allows inflammatory cells to access the brain and further damage it. Therefore, healing the damage to the BBB or protecting the BBB after a traumatic brain injury is vital to the brain after a traumatic brain injury. 

After a traumatic brain injury, the vascular system suffers damage and begins to leak. When blood leaks into tissues, it tends to irritate the tissues and damage them. MSCs release a soluble factor known as TIMP3 tissue metalloproteinase-3 that degrades blood-based proteins known to cause damage to tissues when blood vessels leak. TIMP3 production by MSCs can also protect the BBB from degradation after a traumatic brain injury.

Researchers from the University of Texas Health Sciences Center, UC San Francisco, and two biotechnology companies have examined the protective role of MSCs and one particular protein secreted by MSCs in protecting the BBB after traumatic brain injury.  Shibani Pati, from UC San Francisco, and his collaborators from the University of Texas, Houston, MD Anderson Cancer Center, Amgen, and Blood Systems Research Institute San Francisco used MSCs to staunch the increased permeability the BBB after a traumatic brain injury.  They used a mouse model in these experiments and induced traumatic brain injuries in these mice. Then they gave MSCs to some, and soluble TIMP3 to others, and buffer to another group as a control. They discovered that the MSCs mitigated BBB damage after a traumatic brain injury. However, they also found that soluble TIMP3 could also protect the BBB approximately as well as MSCs. This suggested that the TIMP3 secretion by MSCs is the main mechanism by which MSCs protect the BBB after a traumatic brain injury.

To test this hypothesis, Pati and his colleagues administered MSCs to mice that had experienced traumatic brain injury, but they also co-administered a soluble inhibitor to TIMP3. They discovered that this inhibitor completely abolished the ability of MSCs to protect the BBB after a traumatic brain injury. They also found that the main target of TIMP3 was vascular endothelial growth factor. Apparently after a traumatic brain injury, massive release of vascular endothelial growth factor causes the breakdown of BBB structures. TIMP3 degrades vascular endothelial growth factor, which prevents BBB breakdown.

These findings suggest that administration of recombinant proteins such as TIMP3 after a traumatic brain injury can protect the BBB and decrease brain damage. Clinical trial anyone?

via TIMP3 Secreted by Mesenchymal Stem Cells Protects the Blood Brain Barrier After a Traumatic Brain Injury | Beyond the Dish.

STEM CELLS DEVELOP BEST IN 3D

In STEM CELLS IN THE NEWS on November 24, 2012 at 8:19 am

Scientists have reported improved results for creating insulin-producing cells within a 3 dimensional environment, as opposed to the standard 2 dimension within a Petri dish.  By creating an environment that mimics the inside of an embryo, scientists are able to use this new knowledge to improve diabetes treatment and stem cell treatments for chronic diseases of internal organs.

Scientists from The Danish Stem Cell Center (DanStem) at the University of Copenhagen are contributing important knowledge about how stem cells develop best into insulin-producing cells. In the long-term this new knowledge can improve diabetes treatment with cell therapy. The results have just been published in the scientific journal Cell Reports.

Stem cells are responsible for tissue growth and tissue repair after injury. Therefore, the discovery that these vital cells grow better in a three-dimensional environment is important for the future treatment of disease with stem cell therapy. “We can see that the quality of the cells produced two-dimensionally is not good enough. By putting the cells in a three-dimensional environment and giving them the proper growth conditions, we get much better results. Therefore we are developing a three-dimensional culture medium in gelatine in the laboratory to mimic the one inside an embryo,” says Professor Anne Grapin-Botton from DanStem at the University of Copenhagen, who produced the results together with colleagues from Switzerland and Belgium.

The international research team hopes that the new knowledge about three-dimensional cell growth environments can make a significant contribution to the development of cell therapies for treating diabetes. In the long-term this knowledge can also be used to develop stem cell treatments for chronic diseases in internal organs such as the liver or lungs. Like the pancreas, these organs are developed from stem cells in 3D.

The research team has investigated how the three-dimensional organization of tissue in the early embryonic stage influences development from stem cells to more specialized cells. “We can see that the pancreas looks like a beautiful little tree with branches. Stem cells along the branches need this structure to be able to create insulin-producing cells in the embryo. Our research suggests that in the laboratory beta cells can develop better from stem cells in 3D than if we try to get them to develop flat in a Petri dish,” explains Professor Grapin-Botton.

“Attempts to develop functional beta cells in 2D have unfortunately most often resulted in poorly functioning cells. Our results from developing cells in 3D have yielded promising results and are therefore an important step on the way to developing cell therapies for treating diabetes.”The research is supported by the Novo Nordisk Foundation, Swiss National Research Foundation, and the National Institute of Health (NIH), USA.

The results from the paper “Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis” have just been published in the scientific journal Cell Reports.

http://news.ku.dk/all_news/2012/2012.11/stem_cells_develop_best_in_3d/

NOSE CELL TRANSPLANT ENABLES PARALYSED DOGS TO WALK

In SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on November 22, 2012 at 8:47 am

 

Scientists have reversed paralysis in dogs after injecting them with cells grown from the lining of their nose.  The pets had all suffered spinal injuries which prevented them from using their back legs. The Cambridge University team is cautiously optimistic the technique could eventually have a role in the treatment of human patients.  The study is the first to test the transplant in “real-life” injuries rather than laboratory animals.

The only part of the body where nerve fibres continue to grow in adults is the olfactory system.  Found in the at the back of the nasal cavity, olfactory ensheathing cells (OEC) surround the receptor neurons that both enable us to smell and convey these signals to the brain.  The nerve cells need constant replacement which is promoted by the OECs.

For decades scientists have thought OECs might be useful in spinal cord repair. Initial trials using OECs in humans have suggested the procedure is safe.  In the study, funded by the Medical Research Council and published in Brain, the dogs had olfactory ensheathing cells from the lining of their nose removed.  These were grown and expanded for several weeks in the laboratory.

Of 34 pet dogs on the proof of concept trial, 23 had the cells transplanted into the injury site – the rest were injected with a neutral fluid.  Many of the dogs that received the transplant showed considerable improvement and were able to walk on a treadmill with the support of a harness.  None of the control group regained use of its back legs.  The research was a collaboration between the MRC’s Regenerative Medicine Centre and Cambridge University’s Veterinary School.  Professor Robin Franklin, a regeneration biologist at the Wellcome Trust-MRC Stem Cell Institute and report co-author, 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. Prof. Franklin said, “the procedure might be used alongside drug treatments to promote nerve fibre regeneration and bioengineering to substitute damaged neural networks.”

The researchers say the transplanted cells regenerated nerve fibres across the damaged region of the spinal cord. This enabled the dogs to regain the use of their back legs and coordinate movement with their front limbs.  The new nerve connections did not occur over the long distances required to connect the brain to the spinal cord. The MRC scientists say in humans this would be vital for spinal injury patients who had lost sexual function and bowel and bladder control.

Prof Geoffrey Raisman, chair of Neural Regeneration at University College London, who discovered olfactory ensheathing cells in 1985 said: “This is not a cure for spinal cord injury in humans – that could still be a long way off. But this is the most encouraging advance for some years and is a significant step on the road towards it.”

He said the clinical benefits were still limited: “This procedure has enabled an injured dog to step with its hind legs, but the much harder range of higher functions lost in spinal cord injury – hand function, bladder function, temperature regulation, for example – are yet more complicated and still a long way away.”

Jasper, a 10-year-old dachshund, is one of the dogs which took part in the trial.

His owner May Hay told me: “Before the treatment we used to have to wheel Jasper round on a trolley because his back legs were useless. Now he whizzes around the house and garden and is able to keep up with the other dogs. It’s wonderful.”

 

BBC News – Nose cell transplant enables paralysed dogs to walk.

PLURUIPOTENT STEM CELLS, A POTENTIALLY INVALUABLE THERAPEUTIC RESOURCE

In SCIENCE & STEM CELLS on November 21, 2012 at 7:44 am

B0007671 Mouse embryonic stem cells

Pluripotent stem cells are potentially an invaluable therapeutic resource, as shown in a recent study conducted by the Stanford University School of Medicine.  Within this study, researchers found that with appropriate initial coaching of cells and through the use of environmental cues, the human body has the ability to direct differentiation of cells.

 

Pluripotent stem cells are nature’s double-edged sword. Because they can develop into a dizzying variety of cell types and tissues, they are a potentially invaluable therapeutic resource. However, that same developmental flexibility can lead to dangerous tumors called teratomas if the stem cells begin to differentiate out of control in the body.

To prevent this outcome, researchers must first give the cells a not-so-subtle shove toward their final developmental fate before transplanting them into laboratory animals or humans. But exactly how to do so can vary widely among laboratories. Now researchers at the Stanford University School of Medicine have used an experiment in mice to hit upon a way to possibly skip this fiddly step by instead relying mostly on signals within the body to keep the stem cells in line.

“Before we can use these cells, we have to differentiate, or ‘coach,’ them down a specific developmental pathway,” said Michael Longaker, MD, the Deane P. and Louise Mitchell Professor in the School of Medicine. “But there’s always a question as to exactly how to do that, and how many developmental doors we have to close before we can use the cells. In this study, we found that, with appropriate environmental cues, we could let the body do the work.”

Allowing the body to direct differentiation could speed the U.S. Food and Drug Administration’s approval of using such pluripotent stem cells, Longaker believes, by eliminating the extended periods of laboratory manipulation required during the forced differentiation of the cells.

Longaker, who co-directs Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, is the senior author of the research, published online Nov. 19 in the Proceedings of the National Academy of Sciences. Postdoctoral scholars Benjamin Levi, MD, and Jeong Hyun, MD, and research assistant Daniel Montoro are co-first authors of the work. Longaker is also a member of the Stanford Cancer Institute.

“Once we identify the key proteins and signals coaching the tissue within the body, we can try to mimic them when we use the stem cells,” said Longaker. “Just as the shape of water is determined by its container, cells respond to external cues. For example, in the future, if you want to replace a failing liver, you could put the cells in a scaffold or microenvironment that strongly promotes liver cell differentiation and place the cell-seeded scaffold into the liver to let them differentiate in the optimal macroenvironment

http://med.stanford.edu/ism/2012/november/longaker.html

ADULT STEM CELL POTENTIAL IN REGENERATIVE MEDICINE

In STEM CELLS IN THE NEWS on November 14, 2012 at 7:57 pm

Adipose tissue embolus  Case 104

 

By expanding the use of adipose tissue and its stem cell components, scientist and surgeons have made significant strides in aesthetic and reconstructive surgery. “The opportunities for regenerative medicine interventions based on adult stem cells are tremendous…” – Ivona Percec, MD, PhD

 

As researchers work on reconfiguring cells to take on new regenerative properties, a new review from Penn Medicine plastic surgeons sheds additional light on the potential power of adipose-derived stem cells – or adult stem cells harvested from fatty tissue – in reconstructive and regenerative medicine.

Fat-derived stem cells hold potential for regenerative medicine November 9, 2012 in Surgery (Medical Xpress)—As researchers work on reconfiguring cells to take on new regenerative properties, a new review from Penn Medicine plastic surgeons sheds additional light on the potential power of adipose-derived stem cells – or adult stem cells harvested from fatty tissue – in reconstructive and regenerative medicine.

 

Reconstructive plastic surgeons have clinically integrated “fat grafting” into different surgeries for years, for breast, facial, and other reconstructive and restorative surgeries, with good success. Now, researchers are beginning to understand the power that fatty tissue holds. This new paper, published in the Aesthetic Surgery Journal, enforces that adipose-derived stem cells can be routinely isolated from patients, and once molecular methods are worked out, may be useful for a multitude of regenerative medicine applications. “The opportunities for regenerative medicine interventions based on adult stem cells are tremendous. It is critically important for us to better understand the biology of these cells so that we can develop novel, safe and effective treatments for our patients using their own cells.” said the paper’s senior author, Ivona Percec, MD, PhD, assistant professor in the division of Plastic Surgery in the Perelman School of Medicine at the University of Pennsylvania.

 

Many groups are looking into different modes of isolating and modifying these cells for their regenerative properties, including experts at Penn’s Institute for Regenerative Medicine and around Penn Medicine. For example, Dr. Percec’s team is conducting translational research into the mechanisms controlling adipose-derived stem cells, and how they contribute to the normal human aging process. Stem cells can undergo multiple divisions without differentiation, making them useful tools for cell-replacement therapy. Embryonic stem cells can convert to any cell type, whereas adult stem cells, like the stem cells derived from fat, can differentiate into many, but not all, cell types. A person’s own fat tissue could then potentially be converted into cells specially designed to repair damage to the heart, cartilage, blood vessels, brain, muscle, or bone. As regenerative medicine techniques are refined, experts will continue to explore the utility and benefits of stem cells derived from adipose tissue.

 

Fat Grafting’s Past, Present and Future:  Why Adipose Tissue Is Emerging as a Critical Link to the Advancement of Regenerative Medicine  –  Ivona Percec, MD, PhD

medicalexpress.com

ONE IN THREE OPEN TO TRAVELING FOR MEDICAL TREATMENT

In HEALTH AND WELLNESS on November 14, 2012 at 12:31 pm

airplane

With the globalization of the Medical profession, and the advancements made abroad, medical tourism is becoming more common and accepted. “Various studies using different criteria have estimated that anywhere between 60,000 to 750,000 U.S. residents travel abroad for health care each year, according to the Centers for Disease Control and Prevention.”

NEW YORK | Tue Nov 13, 2012 10:22am EST

NEW YORK(Reuters) – Looking for an affordable face lift without breaking the bank? Want to combine a tummy tuck with two weeks in the sun? You’re not alone. Nearly a third of people surveyed around the world say they are open to the idea of medical tourism – traveling abroad to enjoy cheaper medical or dental treatment, according to a new Ipsos poll of 18,731 adults in 24 countries. Indeed, 18 percent said they would definitely consider it. “The concept of medical tourism is well accepted in many countries,” said Nicolas Boyon, senior vice president of Ipsos Public Affairs.

“With the exception of Japan there are at least one-third of consumers in every country we covered that are open to the idea,” he said in an interview.

Whether for economic reasons or perceptions of superior treatment elsewhere, for treatments ranging from cosmetic to life-saving surgeries, Indians, Indonesians, Russians, Mexicans and Poles were the most open to the idea of being medically mobile. Thirty-one percent or more people in each of those countries said they would definitely consider traveling for a medical or dental treatment.

Conversely, people in Japan, South Korea, Spain and Sweden were least likely to be medical tourists. Boyon said it was not surprising that men and women from emerging nations would be medically mobile if the treatments were cheaper. “This probably reflects perceptions of medical care in other countries that is superior to what is available at home,” he said. But he was intrigued by the percentage of people in developed nations such as Italy, where 66 percent said they would definitely or probably consider medical tourism, along with Germany (48 percent), Canada (41 percent) and the United States, where 38 percent of people were open to the idea.

“It is a reflection that the medical profession is no longer protected from globalization,” Boyon said.

RISKS VS. BENEFITS

Although medical tourism spans a range of treatments, the most common are dental care, cosmetic surgery, elective surgery and fertility treatment, according to a OECD report.

“The medical tourist industry is dynamic and volatile and a range of factors including the economic climate, domestic policy changes, political instability, travel restrictions, advertising practices, geo-political shifts, and innovative and pioneering forms of treatment may all contribute towards shifts in patterns of consumption and production of domestic and overseas health services,” the report said.

Various studies using different criteria have estimated that anywhere between 60,000 to 750,000 U.S. residents travel abroad for health care each year, according to the Centers for Disease Control and Prevention. Along with variations among countries, the Ipsos survey showed that younger adults under 35 years of age were more likely in most countries to consider medical tourism, than people 50 to 64 years old. In India, 86 percent of young adults said they would consider medical tourism, along with 77 percent in China, and 71 percent in Italy.

Boyon suggested that the cost of travel, proximity, borders and quality of care may also be factors considered by potential medical tourists. In both Italy and Germany, about 20 percent of adults said they would definitely consider medical tourism. Both countries are near Hungary, a popular destination for health treatments. Ipsos conducted the poll in Argentina, Australia, Belgium, Brazil, Canada, China, France, Germany, Great Britain, Hungary, India, Indonesia, Italy, Japan, Mexico, Poland, Russia, Saudi Arabia, South Africa, South Korea, Spain, Sweden, Turkey and the United States.

“Ipsos” is a global independent market research company ranking third worldwide among research firms.

http://www.reuters.com/article/2012/11/13/us-medicaltourism-idUSBRE8AC0Q220121113?feedType=RSS&feedName=healthNews

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