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

 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. 

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. 

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

 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.  

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.  

“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

 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

To ease shortage of organs, grow them in a lab?

By the time 10-year-old Sarah Murnaghan finally got a lung transplant last week, she’d been waiting for months, and her parents had sued to give her a better shot at surgery.

Her cystic fibrosis was threatening her life, and her case spurred a debate on how to allocate donor organs. Lungs and other organs for transplant are scarce.

But what if there were another way? What if you could grow a custom-made organ in a lab? 

It sounds incredible. But just a three-hour drive from the Philadelphia hospital where Sarah got her transplant, another little girl is benefiting from just that sort of technology. Two years ago, Angela Irizarry of Lewisburg, Pa., needed a crucial blood vessel. Researchers built her one in a laboratory, using cells from her own bone marrow. Today the 5-year-old sings, dances and dreams of becoming a firefighter — and a doctor.

Growing lungs and other organs for transplant is still in the future, but scientists are working toward that goal. In North Carolina, a 3-D printer builds prototype kidneys. In several labs, scientists study how to build on the internal scaffolding of hearts, lungs, livers and kidneys of people and pigs to make custom-made implants.

Here’s the dream scenario: A patient donates cells, either from a biopsy or maybe just a blood draw. A lab uses them, or cells made from them, to seed onto a scaffold that’s shaped like the organ he needs. Then, says Dr. Harald Ott of Massachusetts General Hospital, “we can regenerate an organ that will not be rejected (and can be) grown on demand and transplanted surgically, similar to a donor organ.”

That won’t happen anytime soon for solid organs like lungs or livers. But as Angela Irizarry’s case shows, simpler body parts are already being used as researchers explore the possibilities of the field.

Just a few weeks ago, a girl in Peoria, Ill., got an experimental windpipe that used a synthetic scaffold covered in stem cells from her own bone marrow. More than a dozen patients have had similar operations.

Dozens of people are thriving with experimental bladders made from their own cells, as are more than a dozen who have urethras made from their own bladder tissue. A Swedish girl who got a vein made with her marrow cells to bypass a liver vein blockage in 2011 is still doing well, her surgeon says.

In some cases the idea has even become standard practice. Surgeons can use a patient’s own cells, processed in a lab, to repair cartilage in the knee. Burn victims are treated with lab-grown skin.

In 2011, it was Angela Irizarry’s turn to wade into the field of tissue engineering.

Angela was born in 2007 with a heart that had only one functional pumping chamber, a potentially lethal condition that leaves the body short of oxygen. Standard treatment involves a series of operations, the last of which implants a blood vessel near the heart to connect a vein to an artery, which effectively rearranges the organ’s plumbing.

Yale University surgeons told Angela’s parents they could try to create that conduit with bone marrow cells. It had already worked for a series of patients in Japan, but Angela would be the first participant in an American study.

“There was a risk,” recalled Angela’s mother, Claudia Irizarry. But she and her husband liked the idea that the implant would grow along with Angela, so that it wouldn’t have to be replaced later.

So, over 12 hours one day, doctors took bone marrow from Angela and extracted certain cells, seeded them onto a 5-inch-long biodegradable tube, incubated them for two hours, and then implanted the graft into Angela to grow into a blood vessel.

It’s been almost two years and Angela is doing well, her mother says. Before the surgery she couldn’t run or play without getting tired and turning blue from lack of oxygen, she said. Now, “she is able to have a normal play day.”

This seed-and-scaffold approach to creating a body part is not as simple as seeding a lawn. In fact, the researchers in charge of Angela’s study had been putting the lab-made blood vessels into people for nearly a decade in Japan before they realized that they were completely wrong in their understanding of what was happening inside the body.

“We’d always assumed we were making blood vessels from the cells we were seeding onto the graft,” said Dr. Christopher Breuer, now at Nationwide Children’s Hospital in Columbus, Ohio. But then studies in mice showed that in fact, the building blocks were cells that migrated in from other blood vessels. The seeded cells actually died off quickly. “We in essence found out we had done the right thing for the wrong reasons,” Breuer said.

Other kinds of implants have also shown that the seeded cells can act as beacons that summon cells from the recipient’s body, said William Wagner, director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. Sometimes that works out fine, but other times it can lead to scarring or inflammation instead, he said. Controlling what happens when an engineered implant interacts with the body is a key challenge, he said.

So far, the lab-grown parts implanted in people have involved fairly simple structures — basically sheets, tubes and hollow containers, notes Anthony Atala of Wake Forest University whose lab also has made scaffolds for noses and ears. Solid internal organs like livers, hearts and kidneys are far more complex to make.

His pioneering lab at Wake Forest is using a 3-D printer to make miniature prototype kidneys, some as small as a half dollar, and other structures for research. Instead of depositing ink, the printer puts down a gel-like biodegradable scaffold plus a mixture of cells to build a kidney layer by layer. Atala expects it will take many years before printed organs find their way into patients.

Another organ-building strategy used by Atala and maybe half a dozen other labs starts with an organ, washes its cells off the inert scaffolding that holds cells together, and then plants that scaffolding with new cells.

“It’s almost like taking an apartment building, moving everybody out … and then really trying to repopulate that apartment building with different cells,” says Dr. John LaMattina of the University of Maryland School of Medicine. He’s using the approach to build livers. It’s the repopulating part that’s the most challenging, he adds.

One goal of that process is humanizing pig organs for transplant, by replacing their cells with human ones.

“I believe the future is … a pig matrix covered with your own cells,” says Doris Taylor of the Texas Heart Institute in Houston. She reported creating a rudimentary beating rat heart in 2008 with the cell-replacement technique and is now applying it to a variety of organs.

Ott’s lab and the Yale lab of Laura Niklason have used the cell-replacement process to make rat lungs that worked temporarily in those rodents. Now they’re thinking bigger, working with pig and human lung scaffolds in the lab. A human lung scaffold, Niklason notes, feels like a handful of Jell-O.

Cell replacement has also worked for kidneys. Ott recently reported that lab-made kidneys in rats didn’t perform as well as regular kidneys. But, he said, just a “good enough organ” could get somebody off dialysis. He has just started testing the approach with transplants in pigs.

Ott is also working to grow human cells on human and pig heart scaffolds for study in the laboratory.

There are plenty of challenges with this organ-building approach. One is getting the right cells to build the organ. Cells from the patient’s own organ might not be available or usable. So Niklason and others are exploring genetic reprogramming so that, say, blood or skin cells could be turned into appropriate cells for organ-growing.

Others look to stem cells from bone marrow or body fat that could be nudged into becoming the right kinds of cells for particular organs. In the near term, organs might instead be built with donor cells stored in a lab, and the organ recipient would still need anti-rejection drugs.

How long until doctors start testing solid organs in people? Ott hopes to see human studies on some lab-grown organ in five to 10 years. Wagner calls that very optimistic and thinks 15 to 20 years is more realistic. Niklason also forecasts two decades for the first human study of a lung that will work long-term.

But LaMattina figures five to 10 years might be about right for human studies of his specialty, the liver.

“I’m an optimist,” he adds. “You have to be an optimist in this job.”

 

Source: AP, Malcolm Ritter, Michael Rubinkam, Allen breed

Mayo Clinc puts stem cells to the test on infant heart defect

Every year, about 1,000 babies are born in the United States with half a heart — a rare defect that requires a series of risky surgeries and, even then, leaves the infants with a strong likelihood that their hearts will wear out prematurely. 

Now, the Mayo Clinic has received federal approval for a first-of-its kind clinical study to see if stem cells from the babies’ own umbilical cords can strengthen their underdeveloped hearts and extend their lives.

If it works, the new technique could buy these children time as scientists scramble for a cure for the congenital defect called hypoplastic left heart syndrome (HLHS).

The Mayo study, which will begin as soon as 10 eligible candidates can be enrolled, could also pave the way for additional breakthroughs in stem cell treatments that would help the 19,000 children born each year with other heart defects. But for the time being, the doctors at Mayo are keeping their focus on those babies who need the most help now.

“We are not here to build an academic career out of science and technology,’’ said Dr. Timothy Nelson, director of Mayo’s HLHS research program. “We’re really here to make a difference in children’s lives who are living today with unmet needs.”

Christina DeShaw of Clive, Iowa, was pregnant with fraternal twins when she learned during an ultrasound procedure that the left side of her daughter’s heart was not developing properly.

“The world just started spinning,” DeShaw said. “Our lives were forever changed from that moment on.”

DeShaw and her husband, Brad Weitl, sought help from the Mayo Clinic for the baby they named Ava Grace.

They learned that children born with defects on the left side of the heart must undergo a series of three complex surgeries. The first is called the Norwood procedure: Within a few days of birth, surgeons reconstruct the heart so that the fully developed right ventricle can do both its own work of supplying blood to the lungs and the work of the defective left ventricle, which ordinarily would pump oxygenated blood back to the body.

Dr. Harold Burkhart, who is overseeing surgeries in Mayo’s new study, said that when the procedure was developed in 1983, only about 30 percent of the patients survived. About 70 percent survive now, he said, and at Mayo, about 9 out of 10 make it through.

The second and third surgeries are much safer. They involve rerouting blood from the body directly to the lungs, bypassing the heart entirely to reduce the workload of the right ventricle.

Ava Grace Weitl was born by Caesarean section on May 8, 2012, then whisked away for her first surgery. “Her heart was the size of a walnut,” DeShaw said. “She had less than a 40 percent chance of making it.”

Ava remained under intensive care until Labor Day. DeShaw, who works at ING Financial Partners in Des Moines, spent months living in a Rochester hotel; her husband, a construction estimator, drove up on weekends. But their trauma didn’t stop when they finally took their daughter home. Ava has suffered numerous complications and once had to be flown back to Mayo in a helicopter.

Unfortunately, Ava won’t be eligible for the stem cell trial: The design calls for stem cells to be injected into the right ventricle during the second surgery, and Ava has already had hers.

Still, Ava’s parents remain dedicated to helping with Mayo’s research. “We wanted to participate, not only because we thought that at some point Ava might benefit, but we also wanted to help all the other babies … and to try to give them the best shot,’’ DeShaw said.

Seeds of life

Cardiac stem cell treatments were pioneered in adult patients. Worldwide, some 5,000 to 6,000 people have received stem cell treatments for heart conditions, but those procedures relied on cells taken from the patients’ bone marrow, said Dr. Atta Behfar, one of Mayo’s leading researchers in the field.

Behfar, working with Dr. Andre Terzic, a Mayo cardiovascular specialist, found that stem cells typically lose their vitality as they age and apparently become “sick” along with the patient. Mayo just finished a clinical trial in Europe showing that they could kick-start those cells in a way that significantly improves the patient’s health, cuts treatment costs and improves quality of life.

Nelson said he thinks stem cells taken from umbilical cord blood and placed into a growing heart will prove even more effective.

“I think of stem cells as seeds,” Nelson said. “If you plant that seed into a rocky, dry soil, that seed may not grow nearly as well as if you plant it into a black, rich, fertile soil that gets watered, irrigated and fertilized,” he said. “And so we think of this as planting these seeds into that fertile soil of a pediatric heart.”

Also, Nelson said, stem cells from the umbilical cord seem to know when to stop producing heart cells, so they don’t create the same cancer concerns that have been associated with the use of “pluripotent” embryonic cells or bioengineered cells in adult hearts.

Too few hearts

Nelson dedicated himself to finding a cure for hypoplastic left heart syndrome when he was studying to become a pediatric heart surgeon. He said it tore him up to know that babies who endured three open heart surgeries would often return as young children with irreparable heart damage and little likelihood of finding a donor heart in time to save them.

Some research suggested that half the children with HLHS don’t make it to their 5th birthday, Nelson said, but there are also children living into their early 20s. “So there are wonderful success stories of the surgical practice,” he said. “But obviously, the percentage of kids born that make it to that stage is far too low.”

Joshua and Sandra Hughes of Ashburn, Va., said they learned about Mayo’s pediatric heart research from a friend. Their 5-year-old daughter, Jaclyn, also has HLHS, and although she gets treated in Washington, D.C., they volunteered to participate in Mayo’s research program.

Jaclyn underwent an MRI last week, and she and her parents each contributed skin tissue for genetic testing and other research. Mayo’s Dr. Patrick O’Leary thanked them for spending two days in Rochester undergoing tests; he showed them images from Jaclyn’s scan and said her heart is performing quite well after her third surgery.

“The stuff they’re working on now may not be available for Jackie,” Sandra Hughes said. “But it may be available for the next generation.”

O’Leary interrupted her, voicing his optimism for the Mayo research.

“It may be available for her, too,” he said.

 

Source: Dan Browning, Star Tribune, Ashley Griffin, Kaiser Health

Stem Cells Reach Standard for Use in Drug Development

 Drug development for a range of conditions could be improved with stem cell technology that helps doctors predict the safety and the effectiveness of potential treatments.

University scientists have been able to generate cells in the laboratory that reach the gold standard required by the pharmaceutical industry to test drug safety.

Generating liver cells

The researchers used stem cell technology to generate liver cells — which help our bodies to process drugs.

They found that the cells were equally effective, reaching the same standard, as cells from human liver tissue currently used to assess drug safety.

These human cells used in drug testing are in short supply and vary considerably due to different donors. As a result they are not an ideal source for drug development.

The stem cell based technique developed in Edinburgh, addresses these issues by offering a renewable production of uniform liver cells in the laboratory.

“Differing genetic information plays a key role in how patients’ livers process drugs. We are now able to efficiently produce human liver cells in the laboratory from different people which model the functional differences in human genetics,” said Dr David Hay, of the Medical Research Centre (MRC) for Regenerative Medicine at the University.

Researchers hope to generate liver cells, containing different DNA to reflect the genetic variations in metabolism found in the population

Such cells could be used to help identify differences in response among patients to certain drugs.

The laboratory-generated liver cells could also be used to screen certain drugs that need close monitoring, to optimise patient treatment.

Scientists are working with Edinburgh BioQuarter, with a view to forming a spin-out company to commercialise the research.

 

Source: sciencedaily.com, University of Edinburgh