Stemaid: The future of medicine

Monday, 28 Jan 2008 12:56

Stroke victims could see their condition improve after receiving stem cell transplants, two separate studies have concluded today.

Both studies saw transplanted stem cells successfully migrate and one noted significant reductions in cell death.

They are published today in the journal Cell Transplantation.

The first, carried out by Korean researchers, transplanted a type of stem cells into animals with stroke and then tracked their progression through magnetic resonance imaging (MRI) at intervals up to ten weeks after transplant.

Dr Jihwan Song said cells showed indications of migration "as early as one or two weeks following transplantation" and at ten weeks the majority of the cells were detected in the core of the area deprived of blood supply.

He argued that the findings "will provide an important tool for developing novel stroke therapies".

In the second study, Canadian and Chinese researchers injected connective tissue cells into animals 24 hours after blood flow was blocked to parts of their brains.

Using laser canning to track markers attached to the cells, the scientists found that within seven days of the injection the cells had migrated into the scar area.

"The animals exhibited significant reductions in scar size and cell death and improvements in neurological function when compared to controls that received no BMSCs [tissue cells]," said lead author Dr Ren-Ke Li.

The researchers concluded that the intravenous delivery of bone marrow-derived cells may enhance tissue repair and the functional recovery after a stroke.

Commenting on the findings, Cell Transplantation associated editor De Cesar Borlongan said: "Both studies lend important support to a growing body of laboratory evidence that bone marrow is a remarkable adult stem cell source for transplant therapy following stroke.

"The non-invasive MRI visualisation of pre-labeled [tissue cells] could become a routine clinical marker for transplanted cells as well as for safety and efficacy."

About 150,000 people are estimated to have a stroke each year in the UK, causing 67,000 deaths.

ScienceDaily (Nov. 24, 2007) — Researchers at the Stanford University
School of Medicine have taken a small but significant step, in mouse studies, toward the goal of transplanting adult stem cells to create a new immune system for people with autoimmune or genetic blood diseases.

The researchers found a way to transplant new blood-forming stem cells into the bone marrow of mice, effectively replacing their immune systems. Many aspects of the technique would need to be adapted before it can be tested in humans, said Irving Weissman, MD, a co-senior author of the study and director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. The work was done on a particular group of mice that are a poor mimic for the human immune system. Still, Weissman suggested the remaining hurdles could eventually be overcome.

When those barriers are surmounted, the benefits are potentially big.

A person with an autoimmune disease such as multiple sclerosis has a defective immune system in which immune cells attack the person's own body. An immune system transplant, much like a liver or heart transplant, would give the person a new system that might not attack the body.

The way to get a new immune system is to transplant new blood-forming stem cells into the bone marrow, where they generate all the cells of the blood. But before transplanting new stem cells, the old ones first must be removed, which is currently done by intensive chemotherapy or radiation. Those processes eliminate the cells of the bone marrow, but also damage other tissue and can cause lasting effects including infertility, brain damage and an increased risk of cancer. A treatment for M.S. at the expense of brain function is hardly an ideal therapy.

Weissman and co-first author Deepta Bhattacharya, PhD, a postdoctoral scholar in Weissman's lab, thought one way around this problem would be
to eliminate only the blood-forming stem cells without affecting bone marrow cells or other tissues. They worked with Agnieszka Czechowicz, first author and medical student, to accomplish that feat by injecting the mice with molecules that latch on to specific proteins on the surface of the blood-forming stem cells, effectively destroying the cells. That technique eliminated the blood-forming stem cells without otherwise harming the mice.

"It is essentially a surgical strike against the blood-forming stem cells," said Weissman, the Virginia & D.K. Ludwig Professor for
Clinical Investigation in Cancer Research. When they transplanted new blood-forming stem cells into the mice, those cells took up residence in the bone marrow and established a new blood and immune system.

In a person with autoimmune disease, that new immune system would likely no longer attack tissues of the body. Likewise, in people with a genetic disorder such as sickle cell anemia, the new blood system would not have the sickle-cell mutation, eliminating the cause of disease. However, the barriers are still significant.

First, the researchers don't know whether the same molecule on human blood-forming stem cells would be the right one to target with a therapy. Also, the mice they used in the study lack a functioning immune system. They'll need to get the therapy working in mice with a normal immune system before they can begin testing the technique in humans.

Although these steps will take time to overcome, Weissman said he considered this work to be the beginning of research that could lead to human studies.

Source: Forbes

WEDNESDAY, Oct. 31 (HealthDay News) -- A new U.S. study involving mice suggests the brain's own stem cells may have the ability to restore memory after an injury.

These neural stem cells work by protecting existing cells and promoting neuronal connections.

In their experiments, a team at the University of California, Irvine, were able to bring the rodents' memory back to healthy levels up to three months after treatment.

The finding could open new doors for treatment of brain injury, stroke and dementia, experts say.

"This is one of the first reports that you can take a stem cell transplantation approach and restore memory," said lead researcher Mathew Blurton-Jones, a postdoctorate fellow at the university. "There is a lot of awareness that stem cells might be useful in treating diseases that cause loss of motor function, but this study shows that they might benefit memory in stroke or traumatic brain injury, and potentially Alzheimer's disease."

In the study, published in the Oct. 31 issue of the Journal of Neuroscience, Blurton-Jones and his colleagues used genetically engineered mice that naturally develop brain lesions. The researchers destroyed cells in a brain area called the hippocampus. These cells are known to be vital to memory formation and it is in this region that neurons often die after injury, the researchers explained.

To test the mice's memory, Blurton-Jones's group conducted place and object recognition tests with both healthy mice and brain-injured mice.

Healthy mice remembered their surroundings about 70 percent of the time, while brain-injured mice remembered it only 40 percent of the time. For objects, healthy mice recalled objects about 80 percent of the time, but injured mice remembered them only 65 percent of the time.

The researchers then injected each mouse with about 200,000 neural stem cells.

They found that mice with brain injuries that received the stem cells now remembered their surroundings about 70 percent of the time -- the same as healthy mice. However, mice that didn't receive stem cells still had memory deficits.

The researchers also found that in healthy mice injected with stem cells, the stem cells traveled throughout the brain. In contrast, stem cells given to injured mice lingered in the hippocampus. Only about 4 percent of those stem cells became neurons, indicating that the stem cells were repairing existing cells to improve memory, rather than replacing the dead brain cells, Blurton-Jones's team noted.

The researchers are presently doing another study with mice stricken with Alzheimer's. "The initial results are promising," Blurton-Jones said. "This has a huge potential, but we have to be cautious about not rushing into the clinic too early."

One expert is optimistic about the findings.

"Putting in these stem cells could eventually help in age-related memory decline," said Dr. Paul R. Sanberg, director of the Center of Excellence for Aging and Brain Repair at the University of South Florida College of Medicine. "There is clearly a therapeutic potential to this."

Sanberg noted that for the process to work with Alzheimer's it has to work with older brains. "There is clearly therapeutic potential in humans, but there are a lot of hurdles to overcome," he said. "This is another demonstration of the potential for neural stem cells in brain disorders."

Murdoch researchers may have unlocked the key to treating the early onset of osteoarthritis.

Osteoarthritis results in loss of cartilage which cannot repair itself after injury and for which there is no effective therapy. Current treatments attempt to alleviate painful symptoms but are unable to preserve the cartilage lining the joint.

Working with Australia's adult stem cell company, Mesoblast Limited (ASX:MSB), the University’s pre-clinical trials of Mesoblast’s patented adult stem cells had shown the therapy to significantly protect cartilage against damage in knee osteoarthritis.

The project’s principal investigator, Professor Rick Read from Murdoch’s School of Veterinary and Biomedical Sciences, said the studies have so far shown promising results.

"We are delighted with the significant cartilage protective effects of Mesoblast's allogeneic (donor unrelated) cells in our large animal model of knee osteoarthritis, without any adverse events of the cells at all," Professor Read said.

The results of the trials signalled Mesoblast's expansion of its clinical applications to inflammatory and degenerative diseases of joint cartilage, such as osteoarthritis, which affect millions of people world-wide.

Mesoblast's cartilage trials evaluated the effectiveness and safety of the company's allogeneic adult stem cells to treat osteoarthritis of the knee in 48 arthritic sheep joints.

The results showed that osteoarthritic sheep knee joints receiving Mesoblast's stem cells had significantly greater thickness of joint cartilage, reduced cartilage breakdown, and greater biomechanical strength three months later than did control joints receiving hyaluronic acid.

Mesoblast's Vice President of the Cartilage Regenerative Programs, Professor Peter Ghosh, a world-renowned expert in diseases of cartilage, said the results obtained at three months were very encouraging.

"Professor Read’s team at Murdoch University has been involved for almost 20 years in the development and refinement of this model for investigating new treatments for osteoarthritis,” Professor Ghosh said.

“We are very excited by the results of these studies using adult stem cells."

Professor Read said the project was another example of a productive collaboration between the University’s research experts and the industry.

27-Mar-2007

OAK BROOK, Ill. For the first time, researchers have used adult bone marrow stem cells to regenerate healthy human liver tissue, according to a study published in the April issue of the journal Radiology.

When large, fast-growing cancers invade the liver, some patients are unable to undergo surgery, because removing the cancerous tissue would leave too little liver to support the body.

Researchers at Heinrich-Heine-University in D sseldorf, Germany, used adult bone marrow stem cells to help quickly regenerate healthy liver tissue, enabling patients to eventually undergo a surgical resection.

Our study suggests that liver stem cells harvested from the patient s own bone marrow can further augment and accelerate the liver s natural capacity to regenerate itself, said G nther F rst, M.D., co-author and professor of radiology.

In the study, researchers compared the results of portal vein embolization (PVE), a technique currently used to help regenerate liver tissue, to a combination of PVE and an injection of bone marrow stem cells into the liver.

PVE blocks blood flow to the diseased portion of the liver and diverts blood to the organ s healthy tissue, promoting liver growth. Bone marrow stem cells extracted from the patient s hip bone and injected into the liver also help the liver regenerate.

The study included 13 patients with large central liver malignancies who were unable to undergo surgery because resection would leave less than 25 percent of their total liver volume.

Six of the patients underwent both PVE and injection of bone marrow stem cells. Seven patients underwent only PVE. Computed tomography (CT) scans were performed before and up to five weeks after PVE to determine the degree of liver growth.

Patients who received the combination of PVE and stem cell injection had double the liver growth rate and gain in liver volume, compared with those who underwent PVE alone. As a result, the patients who received the combined treatment were able to undergo surgery an average of 18 days sooner than patients who received PVE only.

Our research demonstrates that stem cells are a powerful adjunct to PVE for patients undergoing surgical resection, said Jan Schulte am Esch, M.D., co-author and surgery staff member. Based on our results, we also believe that adult stem cell administration may be a promising therapy for regenerating livers damaged by other chronic and acute diseases.

2007/3/13
By Maggie Fox, Health and Science Editor WASHINGTON, Reuters

Human stem cells taken from both embryos and fetuses delayed a fatal brain and nerve disease in mice, moving throughout the brain to take on the jobs of damaged neurons, scientists reported on Sunday.
They said their study, published in the journal Nature Medicine, represents the first time a human embryonic stem cell has successfully treated a disease in an animal.

Dr. Evan Snyder of the Burnham Institute for Medical Research in La Jolla, California, who led the study, says his team hopes to move quickly to test their method in children with a fatal and incurable brain disease called Sandhoff disease.

Writing in the journal Nature Medicine, they also said their approach could lead to ways to treat a range of neurodegenerative diseases such as Parkinson's, Alzheimer's and amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease.

For their study, Snyder and colleagues used mice bred with the equivalent of Sandhoff disease.

"Children with the disease have severe mental retardation and motor dysfunction, and death typically occurs in infancy," the researchers, who included a team at Oxford University in Britain, Yonsei University in Seoul, Korea and elsewhere, wrote in their report.

It is marked by inflammation that kills brain cells.

Snyder's team used both human embryonic stem cells, taken from days-old human embryos left over at fertility clinics, and human fetal stem cells.

They transplanted these into the brains of the mice and noted no problems. No tumors formed, the mice did not "reject" the foreign cells, and the treatment seemed to reduce inflammation.

"They just don't seem to get rejected," Snyder said.

The treated mice lived 70 percent longer than untreated mice. The disease eventually came back, but Snyder believes they could keep it at bay by giving booster injections of the stem cells to take over the functions of the mutated natural brain cells.

Stem cells are valued because they can give birth to a range of tissue and cell types. But Snyder said scientists are beginning to learn they do even more than this.

"This shows that stem cells engage in cross-talk," he said in a telephone interview.

"They collaborate ... to try to restore a system to balance. They secrete factors that are healthy. They try to restore the health of other cells and detoxify the system."

The transplanted human cells replaced damaged nerve cells and carried nerve signals. They also boosted the brain's supply of the enzyme hex, which is lacking in Sandhoff disease.

Sandhoff is caused by a mutation in the gene for an enzyme called hexosaminidase or hex, which brain cells need to get rid of excess fatty material called lipids.

When the lipids build up, brain cells die. It is similar to Tay-Sachs disease, and there is no treatment for either Tay-Sachs or Sandhoff.

The use of human embryonic stem cells is controversial because some people believe it is wrong to destroy human embryos in experiments.

Snyder said his team used batches of stem cells approved for funding by the U.S. government. He said when his team asks the U.S. Food and Drug Administration for permission to test the treatment on children, they will probably not seek to use the embryonic stem cells at first, but merely the fetal stem cells.

"I think they are a little bit squeamish," he said.

SAN FRANCISCO -- Stefan Heller's dream is to someday find a cure for deafness.

As a leader in stem cell-based research on the inner ear at the Stanford University School of Medicine, he's got a step-by-step plan for making this dream a reality.

It may take another decade or so, but if anyone can do it, he's the guy to place your bets on.

"Everyone asks, 'How long before we do this?'" said Heller, PhD, associate professor of otolaryngology, whose accent still bears the trace of his native Germany. "I tell them the devil is in the details."

But even at the national level, those in the research community remain hopeful that Heller's work will reap successes sooner rather than later. Heller will discuss his stem cell research during a panel discussion Feb. 17 in San Francisco at the annual meeting of the American Association for the Advancement of Science. The session is titled "Hearing health: The looming crisis and what can be done about it."

James Battey, MD, director of the National Institute on Deafness and Other Communication Disorders, lauded Heller as "one of the leading auditory neuroscientists" and points to his stem cell regeneration research as a high priority for the institute.

Heller's vision is to develop a variety of possible cures for deafness. For the past year and a half, since coming to Stanford from Harvard, he's been focused on two paths: drug therapy -which could be as simple as an application of ear drops - and stem cell transplantation into the inner ear to remedy hearing loss.

Currently he's working on perfecting the steps toward eventual stem cell transplantation into humans, with the goal of first curing deafness in mice within the next five years. His lab is also busy studying the ability of birds to regenerate the tiny hair cells in the cochlea. It's these cells that convert the mechanical energy of sound into electrical impulses that are sent to the brain so that a chicken, a mouse or a human can hear. Chickens, like all birds, have the ability to spontaneously regenerate these hair cells, which explains why there are no deaf birds.

"This is promising because it means the genetic program for regeneration exists somewhere in the vertebrate family," Heller said. "We know there is an unknown signal to regenerate that we could use, but we first have to find it."

The idea of using drug therapy to cure deafness has been at the back of Heller's mind since he began researching the inner ear 12 years ago, and it has become more plausible as a result of his lab's successes in the field of stem cell research during the past seven years.

Heller gained international attention in 2003 for identifying stem cells that reside within the inner ear. Since then, his research has focused on using these stem cells to regenerate the critically needed hair cells in the inner ear. Later in 2003, his group reached another significant milestone: the team demonstrated that it is possible to coax embryonic stem cells in a test tube to differentiate into hair cells - and then also to have the stem cells differentiate after transplantation in the ears of chicken embryos.

The two different approaches - new drugs and stem cell transplants - are important because drug treatments are unlikely to help everyone. For some people with genetically caused hearing disorders, he explained, no drug is likely to help. "For them, stem cell transplantation may be the answer," he said

But for the majority of those with hearing loss, particularly in the aging population, drug therapy could be the solution. As the population has aged and noise pollution has grown more severe, health experts now estimate that one in three adults over the age of 65 has developed a handicapping hearing loss.

Coming up with the answers is a slow process, Heller said. "This research takes time and money, but we remain hopeful we'll have some principle answers soon."

June 20, 2006 11:25 a.m. EST

Richard Rittierodt - All Headline News Staff Writer

Washington DC (AHN) - According to U.S. researchers, paralyzed rats have been able to move again after being given stem cells from mouse embryos.

Dr. Douglas Kerr of The Johns Hopkins University School of Medicine says, "This study provides a 'recipe' for using stem cells to reconnect the nervous system. It raises the notion that we can eventually achieve this in humans, although we have a long way to go ... We found that we needed a combination of all of the treatments in
order to restore function."

Kerr and his colleagues all stated that the transplanted cells, with the right mix of compounds, helped paralyzed rats use their hind legs after some of their nerve cells were regrown.

Dr. Elias Zerhouni, director of the National Institutes of Health, says, "This work is a remarkable advance that can help us understand how stem cells might be used to treat injuries and disease and begin to fulfill their great promise."

Johns Hopkins study could assist people, be a key to funding

Wednesday, July 25, 2001

By Michael Woods, Block News Alliance

BAR HARBOR, Maine -- Johns Hopkins University scientists yesterday reported using human stem cells to restore the ability to walk in rats and mice paralyzed by nerve damage like that found in several human diseases.

"So far as we know, this is the first time human stem cells have produced recovery from a disease in any animal, " said head researcher, Dr. John P. Gearhart.

Gearhart, an internationally known stem cell authority, said the achievement addresses one of the major objections to federal funding for stem cell research.

Human embryonic stem cells are "building block" cells that develop into every other kind of cell found in the body. Researchers believe they can make replacements for body tissue lost to disease or injury -- including whole new hearts, kidneys and other organs for transplantation.

Nevertheless, the federal government has refused to fund embryonic stem cell research because aborted fetuses are a major source of the cells. They can be obtained in other ways, one of which involves destroying human embryos stored in fertility clinics.

The Hopkins research was done with stem cells obtained from human fetuses aborted at 5-8 weeks of age.

One argument against federal funding, Gearhart noted, is that human stem cells have not yet been shown effective in treating a disease. The new findings weaken that argument, he said.

"It's one thing to see evidence that stem cells work in laboratory culture diseases, " Gearhart said at a renowned conference on genetics, this year's being the 42nd Short Course in Medical and Experimental Mammalian Genetics. "And it's quite another to see actual function restored in an animal."

Videos showed the reversal of paralysis in the laboratory animals to be dramatic. Researchers injected human neural stem cells into the spinal fluid of about 80 rats and mice paralyzed by a virus that attacks and destroys nerve cells that control muscle movement.

Normally, animals infected with the Sindbis virus permanently lose the ability to move their limbs, as neurons leading from the spinal cord to muscles deteriorate. Animals drag limp legs and feet behind them.

All of the animals treated with human embryonic stem cells recovered the ability to walk, although not with a normal gait.

Researchers believe the cells may have reversed paralysis in two ways. They may have grown into new rodent nerve cells that replaced the cells killed by the Sindbis virus or they may have produced chemicals that signaled the rodent nerve cells to start growing.

Rodents infected with Sindbis virus are used as a model for spinal motor atrophy. It is the most common inherited neurological disease and the most common inherited cause of infant death.

SMA affects as many as 1 in 6,000 infants, causing nerves leading from the spinal cord to the muscles to deteriorate. Children with SMA are born weak, have difficulty swallowing, breathing and walking. Most die in infancy, although some live into early childhood.

Gearhart said stem cell research may have its most immediate application in treating SMA and a related condition, amyotrophic lateral sclerosis, also called Lou Gehrig's disease.

ALS affects up to 20,000 adults, leading to whole-body paralysis and death as motor nerves linking the brain, spinal cord and muscles die.

Project ALS, a New York City organization that battles the disease, funded the Hopkins research. The treatment could be tested on humans within a few years, Gearhart said.

He predicted the ethical and religious concerns over stem cell research will vanish as scientists discover ways of making different kinds of cells without using embryos. But he emphasized that federal funding of embryonic stem cell research is essential to developing those alternative techniques -- a step that could take 10 years with ample funding and longer without it.