Stem Cells Help Repair Traumatic Brain Injury by Building ‘Biobridge’

brain University of South Florida researchers have suggested a new view of how stem cells may help repair the brain following trauma. In a series of preclinical experiments, they report that transplanted cells appear to build a “biobridge” that links an uninjured brain site where new neural stem cells are born with the damaged region of the brain.

Their findings were recently reported online in the peer-reviewed journal PLOS ONE.

“The transplanted stem cells serve as migratory cues for the brain’s own neurogenic cells, guiding the exodus of these newly formed host cells from their neurogenic niche towards the injured brain tissue,” said principal investigator Cesar Borlongan, PhD, professor and director of the USF Center for Aging and Brain Repair.

Based in part on the data reported by the USF researchers in this preclinical study, the U.S. Food and Drug Administration recently approved a limited clinical trial to transplant stem cells in patients with traumatic brain injury.

Stem cells are undifferentiated, or blank, cells with the potential to give rise to many different cell types that carry out different functions. While the stem cells in adult bone marrow or umbilical cord blood tend to develop into the cells that make up the organ system from which they originated, these multipotent stem cells can be manipulated to take on the characteristics of neural cells.

To date, there have been two widely-held views on how stem cells may work to provide potential treatments for brain damage caused by injury or neurodegenerative disorders. One school of thought is that stem cells implanted into the brain directly replace dead or dying cells. The other, more recent view is that transplanted stem cells secrete growth factors that indirectly rescue the injured tissue.

The USF study presents evidence for a third concept of stem-cell mediated brain repair.

The researchers randomly assigned rats with traumatic brain injury and confirmed neurological impairment to one of two groups. One group received transplants of bone marrow-derived stem cells into the region of the brain affected by traumatic injury. The other received a sham procedure in which solution alone was infused into the brain with no implantation of stem cells.

At one and three months post-TBI, the rats receiving stem cell transplants showed significantly better motor and neurological function and reduced brain tissue damage compared to rats receiving no stem cells. These robust improvements were observed even though survival of the transplanted cells was modest and diminished over time.

The researchers then conducted a series of experiments to examine the host brain tissue.

At three months post-traumatic brain injury, the brains of transplanted rats showed massive cell proliferation and differentiation of stem cells into neuron-like cells in the area of injury, the researchers found. This was accompanied by a solid stream of stem cells migrating from the brain’s uninjured subventricular zone — a region where many new stem cells are formed — to the brain’s site of injury.

In contrast, the rats receiving solution alone showed limited proliferation and neural-commitment of stem cells, with only scattered migration to the site of brain injury and virtually no expression of newly formed cells in the subventricular zone. Without the addition of transplanted stem cells, the brain’s self-repair process appeared insufficient to mount a defense against the cascade of traumatic brain injury-induced cell death.

The researchers conclude that the transplanted stem cells create a neurovascular matrix that bridges the long-distance gap between the region in the brain where host neural stem cells arise and the site of injury. This pathway, or “biobridge,” ferries the newly emerging host cells to the specific place in the brain in need of repair, helping promote functional recovery from traumatic brain injury.

Source: http://www.sciendedaily.com, University of South Florida


Patient’s Own Cells Might Be Used As Treatment For Parkinson’s Disease

Induced pluripotent stem cells (iPSCs) taken from a patient hold great therapeutic potential for many diseases. However, studies in rodents have suggested that the body may mount an immune response and destroy cells derived from iPSCs. New research in monkeys refutes these findings, suggesting that in primates like us, such cells will not be rejected by the immune system. In the paper, publishing September 26 in the ISSCR’s journal Stem Cell Reports, published by Cell Press, iPSCs from nonhuman primates successfully developed into the neurons depleted by Parkinson’s disease while eliciting only a minimal immune response. The cells therefore could hold promise for successful transplantation in humans. reach

iPSCs are cells that have been genetically reprogrammed to an embryonic stem-cell-like state, meaning that they can differentiate into virtually any of the body’s different cell types. iPSCs directed to differentiate into specific cell types offer the possibility of a renewable source of replacement cells and tissues to treat ailments, including Parkinson’s disease, spinal cord injury, heart disease, diabetes, and arthritis.

Studies in rodents have suggested that iPSC-derived cells used for transplantation may be rejected by the body’s immune system. To test this in an animal that is more closely related to humans, investigators in Japan directed iPSCs taken from a monkey to develop into certain neurons that are depleted in Parkinson’s disease patients. When they were injected into the same monkey’s brain (called an autologous transplantation), the neurons elicited only a minimal immune response. In contrast, injections of the cells into immunologically unmatched recipients (called an allogeneic transplantation) caused the body to mount a stronger immune response.

“These findings give a rationale to start autologous transplantation—at least of neural cells—in clinical situations,” says senior author Dr. Jun Takahashi, of the Kyoto University’s Center for iPS Cell Research and Application. The team’s work also suggests that transplantation of such neurons into immunologically matched recipients may be possible with minimal use of immunosuppressive drugs.

 

Source: http://www.redorbit.com, Cell Press


Regenerative medicine and stem cells focus of Mayo Clinic heart research

Researchers at Mayo Clinic in Rochester are looking for new ways to repair a heart that doesn’t beat properly in the days following a heart attack. heart

Traditionally, a person with an irregular heartbeat — a problem known medically as dyssynchrony — gets treated with a pacemaker to coach the heart back into normal rhythm.

But that’s ineffective for about a third of patients, said Dr. Andre Terzic, director of the Mayo Clinic Center for Regenerative Medicine.

That’s why researchers at Mayo turned their gaze toward regenerative medicine and adult stem cells, the kind that can be guided to become most any type of tissue.

The team has demonstrated in a proof-of-concept experiment that heart rhythm disruptions after a heart attack can be fixed with regenerative medicine.

The researchers conducted early-stage research with mice, which means there’s much study yet to be done. Although mouse studies do not always translate well for application into humans, the study, Terzic said, shows that it’s possible to repair a heart’s rhythm with stem cells.

“This extends the work that we are doing in defining what could be the most-useful applications for regenerative medicine,” whose team has already begun clinical trials in humans and has the ability to coax a patient’s own stem cells to become potentially reparative heart tissue.

The new study in mice “introduces — for the first time — stem cell-based ‘biological re-synchronization’ as a novel means to treat cardiac dyssynchrony,” Terzic said in a Mayo announcement.

It will take time to translate what has been found into use for humans, Terzic said in an interview with the Post-Bulletin. But, in the meantime, researchers can begin looking for signs of re-synchronization in other ongoing research studies, he said.

Heart chambers must beat in synchrony to ensure the proper pumping, which is why the possibility of stem-cell treatment when pacemakers don’t work seems so enticing.

“Typically one-third of patients do not respond favorably to pacing,” Terzic said. “So there is an absolute ‘must’ to find a solution for that one-third.”

Increasingly, he said, regenerative-medicine research considers the body’s own ability to heal and looks for ways to boost it. The new study, published in The Journal of Physiology, could change regenerative medicine’s concept of what is possible, if the current results get confirmed.

“We have developed essentially a new area of medicine of ‘biological re-synchronization,'” Terzic said. “We take advantage of stem cells to repair, rather than taking advantage of a device just to pace…in other words, the solution is coming from our own cells.”

Terzic said the study is but one example of what is essentially merging regenerative medicine with individualized medicine — picking a stem-cell or other regenerative-medicine treatment that will work best for a specific individual.

“We have seen major advances in what we call cardiac regeneration medicine. We started initially as science fiction and eventually over the years it has become reality,” Terzic said. “We have already brought it to patients.”

Mayo in Rochester, Florida and Arizona have current clinical trials for patients dealing with health medical conditions like Lou Gehrig’s disease, gastrointestinal issues, heart attack, angina, Crohn’s disease, multiple-system atrophy, kidney disease and pediatric heart problems. Study continues with orthopedics (could a hip bone be triggered to heal instead of needing surgery?), diabetes (what if a patient’s own cells could be triggered to become insulin-producers?) and neurology.

These days, patients of all ages who connect with Mayo directly or through their health provider can get referred to the Regenerative Medicine Clinic for consultation about options.

The idea is to fulfill the unmet needs of patients. Not to extend life, but to extend healthy life, Terzic said.

“That is the holy grail,” he said.

Source: Jeff Hansel http://www.medcitynews.com, http://www.postbulletin.com


Stem cells help offset brain damage from stroke

bone marrow stem cells Cognitive deficits following ischemic stroke are common and debilitating, even in the relatively few patients who are treated expeditiously so that clots are removed or dissolved rapidly and cerebral blood flow restored.

A new study in Restorative Neurology and Neuroscience demonstrates that intracerebral injection of bone-marrow-derived mesenchymal stem cells (BSCs) reduces cognitive deficits produced by temporary occlusion of cerebral blood vessels in a rat model of stroke, suggesting that BSCs may offer a new approach for reducing post-stroke cognitive dysfunction.

According to the American Heart Association, almost half of ischemic stroke survivors older than 65 years of age experience cognitive deficits, contributing to functional impairments, dependence, and increased mortality. The incidence of cognitive deficits triples after stroke and about one quarter of cognitively impaired stroke patients’ progress to dementia. For these reasons, “there is an underlying need for restorative therapies,” says lead investigator Gary L. Dunbar, PhD, of the Field Neurosciences Institute Laboratory for Restorative Neurology, and Director of the Central Michigan University Program in Neuroscience.

In order to see whether mesenchymal stem cells derived from bone marrow could attenuate or prevent cognitive problems following a stroke-like ischemic event, the investigators mimicked stroke in rats by injecting the hormone endothelin-1 (ET-1) directly into the brain in order to constrict nearby blood vessels and block blood flow temporarily. Control animals underwent similar surgery but were injected with saline, not ET-1.

Seven days after the “stroke”, some of the rats received intrastriatal injections of BSC, while others received control injections. Cognition was evaluated using a spatial operant reversal task (SORT), in which the animals were trained to press a lever a certain number of times when it was illuminated to receive a food reward.

The investigators found that animals that underwent a stroke but were then injected with BSC made significantly fewer incorrect lever presses than stroke rats who received control injections. In fact, the BSC-treated stroke animals performed as well as those who did not have a stroke. “Importantly, there were no significant between-group differences in the total number of lever presses, indicating the deficits observed were cognitive, rather than motor in nature,” said Dr. Dunbar. No differences were observed in infarct size between the BMMSC-treated and control groups.

The authors emphasize that the BMMSCs were effective even when transplanted seven days after the induced stroke, a finding that offers hope to patients who may not present for treatment immediately. The authors suggest that BMMSCs may work by creating a microenvironment that provides trophic support to remaining viable cells, perhaps by releasing substances such as brain-derived neurotrophic factor (BDNF).
Source: ScienceBlog, http://www.scienceblog.com


Special type of stem cells could help heal hearts

About 5.8 million Americans have heart failure, a condition that occurs when the heart can no longer pump enough blood to meet the body’s needs.

Now, researchers say a special type of stem cell may be the key to repairing these hearts. Golf has always been a big part of Ron Signorelli’s life.

“I started when I was ten,” Ron said.  Painted heart

However, Ron’s congestive heart failure was keeping him away from his favorite pastime.

“I was in the hospital over 20 times,” Ron said.

Ron’s heart pumped only 15 percent of blood. He needed help fast.

“There’s a large number of patients out there that are really in this situation where they’re gone past what normal medical therapy can do, but yet they’re not sick enough or don’t qualify for a heart transplant,” Timothy D. Henry, MD, Director of Research Minneapolis Heart Institute Foundation said.

Now, a new approach can help patients like Ron. First, doctors extract bone marrow stem cells from the patient. Then, they grow the cells to enhance their healing ability. Those cells are then injected directly into the patient’s heart.

“Our hopes are we improve the quality of their life, as well as the length of their life,” Dr. Henry said.

In the first clinical trial, the treatment was safe, repaired damaged heart muscles, and even appeared to reverse some heart failure symptoms. Ron had 12 injections and hasn’t been to the hospital since.

“I certainly feel good. I’m a very active person,” Ron said. Now, nothing stops his stride. “When the weather is nice, I’ll play three, four times a week,” Ron explained.

Researchers are planning enrollment for the second phase of this trial at about 30-sites across the U.S. Once the results are assessed, the treatment will likely be more widely available. This therapy would not replace a heart transplant, but may delay or prevent the need for transplantation in the future.

Source: Margot Kim, http://www.abclocal.go.com


Use stem cells for custom blood vessels

Engineers have coaxed stem cells into forming networks of new blood vessels, then successfully transplanted them into mice.  bloodvessels_1

“That these vessels survive and function inside a living animal is a crucial step in getting them to medical application,” says Sravanti Kusuma, a biomedical engineering graduate student at Johns Hopkins University.

The human stem cells used in the experiment were made by reprogramming ordinary cells, so the new technique could potentially be used to make blood vessels genetically matched to individual patients and unlikely to be rejected by their immune systems, investigators say.

Human blood vessel networks, in red, grown in a lab from stem cells and then transplanted into a mouse, are seen incorporating themselves into and around networks of the mouse’s vessels, in green. (Credit: PNAS)

Custom-made blood vessel networks could help patients with burns, complications of diabetes, or other conditions that compromise blood flow.

“In demonstrating the ability to rebuild a microvascular bed in a clinically relevant manner, we have made an important step toward the construction of blood vessels for therapeutic use,” says Sharon Gerecht, associate professor of chemical and biomolecular engineering.

Blood vessels have previously been grown in the laboratory using stem cells, but barriers remained to efficiently producing the vessels and using them to treat patients.

For the latest study, published in Proceedings of the National Academy of Sciences, researchers focused on streamlining the process. Where other experiments used chemical cues to get stem cells to form cells of a single type, or to mature into a smorgasbord of cell types that the researchers would then sort through, Kusuma devised a way to get the stem cells to form the two cell types needed to build new blood vessels—and only those types.

“It makes the process quicker and more robust if you don’t have to sort through a lot of cells you don’t need to find the ones you do, or grow two batches of cells,” Kusuma says.

Elegant use of cells

A second difference from previous experiments was that instead of using adult stem cells derived from cord blood or bone marrow to construct the network of vessels, Gerecht’s group teamed with Linzhao Cheng, a professor in the Institute for Cell Engineering, to use induced pluripotent stem cells as their starting point.

Since this type of cell is made by reverse-engineering mature cells—from the skin or blood, for example—using it means that the resulting blood vessels could be tailor-made for specific patients.

“This is an elegant use of human induced pluripotent stem cells that can form multiple cell types within one kind of tissue or organ and have the same genetic background,” Cheng says.

“This study showed that in addition to being able to form blood cells and neural cells as previously shown, blood-derived human induced pluripotent stem cells can also form multiple types of vascular network cells.”

To grow the vessels, the research team put stem cells into scaffolding made of a squishy material called hydrogel. The hydrogel was loaded with chemical cues that nudged the cells to organize into a network of recognizable blood vessels made up of cells that create the network and the type that support and give vessels their structure.

This was the first time that blood vessels had been constructed from human pluripotent stem cells in synthetic material.

To learn whether the vessel-infused hydrogel would work inside a living animal, the group implanted it into mice. After two weeks, the lab-grown vessels had integrated with the mice’s own vessels; the hydrogel had begun to biodegrade and disappear as designed.

One of the next steps, Kusuma says, will be to look more closely at the 3D structures the lab-grown vessels form. Another will be to see whether the vessels can deliver blood to damaged tissues and help them recover.

The study was funded by the American Heart Association, the National Heart, Lung, and Blood Institute, the National Cancer Institute, and the National Science Foundation.

 

Source: Shawna Williams, Johns Hopkins, Johns Hopkins University


No more root canals? Scientists aim to regrow teeth using stem cells

Dental Could the days of the root canal, for decades the symbol of the most excruciating kind of minor surgery, finally be numbered?

Scientists have made advances in treating tooth decay that they hope will let them restore tooth tissue—and avoid the painful dental procedure. Several recent studies have demonstrated in animals that procedures involving tooth stem cells appear to regrow the critical, living tooth tissue known as pulp.

Treatments that prompt the body to regrow its own tissues and organs are known broadly as regenerative medicine. There is significant interest in figuring out how to implement this knowledge to help the many people with cavities and disease that lead to tooth loss.

In the U.S., half of kids have had at least one cavity by the time they are 15 years old and a quarter of adults over the age of 65 have lost all of their teeth, according to the Centers for Disease Control and Prevention. An estimated $108 billion was spent on dental services in 2010, including elective and out-of-pocket care, according to the CDC.

Tooth decay arises when bacteria or infections overwhelm a tooth’s natural repair process. If the culprit isn’t reduced or eliminated, the damage can continue. If it erodes the hard, outer enamel and penetrates down inside the tooth, the infection eventually can kill the soft pulp tissue inside, prompting the need for either a root canal or removal of the tooth. Pulp is necessary to detecting sensation, including heat, cold and pressure, and contains the stem cells—undifferentiated cells that turn into specialized ones—that can regenerate tooth tissue.

Researchers from South Korea and Japan to the U.S. and United Kingdom have been working on how to coax stem cells into regenerating pulp. The process is still in its early stages, but if successful, it could mean a reduction or even elimination of the need for painful root canals.

While much of the work has shown promise in the lab and in early work in animals, including dogs, there have only been a few reports of experiments in humans.

The root-canal procedure involves cleaning out the infected and dead tissue in the root canal of the tooth, disinfecting the area and adding an impermeable seal to try to prevent further infection.

But the seal does not always prevent new infection. While the affected tooth remains in the mouth, it is essentially dead, which could impact functions like chewing. That also means no living nerves remain in the tooth to detect further decay or infection. Infection could subsequently spread to surrounding tissue without detection. An estimated 15.1 million root canals are performed in the U.S. annually, according to a 2005-06 survey by the American Dental Association, the most recent data available.

“The whole concept of going for pulp regeneration is that you will try and retain a vital tooth, a tooth that is alive,” says Tony Smith, a professor in oral biology at the University of Birmingham in the U.K. “That means the tooth’s natural defense mechanisms will still be there.

“I think we are really just at the opening stages of what is going to be a very exciting time, because we’re moving away from traditional root-canal treatments.”

Some scientists have focused on growing entirely new teeth. More are focused on trying to grow healthy new pulp inside the hard shell of tooth enamel, either by stimulating or encouraging stem cells or by better controlling the inflammation that goes on in the mouth in response to an infection.

Some of the challenges with making new teeth are generating not just the right tissue but also the right structure, as well as how to place the tooth or the new pulp in the mouth, according to Rena D’Souza, a professor of biomedical sciences at Baylor College of Dentistry. Beyond anti-inflammatory medication, options for tackling the infection while the new treatments work are limited. And, as with stem-cell research efforts with other body parts, successfully regenerating dental tissue in the lab or another animal doesn’t mean it will work in a human body.

Dental stem cells can be harvested from the pulp tissue of the wisdom and other types of adult teeth, or baby teeth. They can produce both the hard tissues needed by the tooth, like bone, and soft tissues like the pulp, says Dr. D’Souza, a former president of the American Association for Dental Research who will become the dean of the University of Utah’s School of Dental Medicine Aug. 1.

She and colleagues at Baylor and Rice University focused on regrowing pulp using a small protein hydrogel. The gelatin-like substance is injected into the tooth and serves as a base into which pulp cells, blood vessels and nerves grow.

In a study published in November, they were able to demonstrate pulp regeneration in human teeth in a lab. They will soon be testing hydrogel on live dogs. In addition, they are looking at the potential of the hydrogel to calm dental inflammation.

Source: http://www.foxnews.com, Smarter America, The Wall Street Journal


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