Category Archives: Stem Cell Videos

Neurons (in yellow) derived from human embryonic stem cells have restored hearing to deaf gerbils.

Marcelo Rivolta, University of Sheffield

More than 275 million people have moderate-to-profound hearing loss, and many of those cases are caused by a breach in the connection between the inner ear and the brain.

Researchers have now shown how to repair a key component of that connection the auditory nerve by using human embryonic stem cells to restore hearing in gerbils1. "We have the proof of concept that we can use human embryonic stem cells to repair the damaged ear," says lead author Marcelo Rivolta, a stem-cell biologist at the University of Sheffield, UK, whose research appears in Nature today. "More work needs to be done, but now we know it's possible."

Stem cells have been differentiated into auditory nerve cells before, but this is the first time that transplanted cells have successfully restored hearing in animals. Some in the field say that it is a pivotal step that will undoubtedly spur more research. Research has been stymied by reviewers wanting evidence that stem cells can connect the inner ear to the central nervous system, says Richard Altschuler, a developmental biologist at the Kresge Hearing Research Institute at the University of Michigan in Ann Arbor.

Rivolta has spent the past decade developing ways to differentiate human embryonic stem cells into the two cell types that are essential for hearing: auditory neurons, and the inner-ear hair cells that translate sound into electrical signals.

He treated human embryonic stem cells with two types of fibroblast growth factor (FGF) FGF3 and FGF10 to produce two, visually distinct, groups of primordial sensory cell. Those that had characteristics similar to hair cells were dubbed otic epithelial progenitors (OEPs), and those that looked more like neurons were dubbed otic neural progenitors (ONPs).

His team then transplanted ONPs into the ears of gerbils that had been treated with ouabain, a chemical that damages auditory nerves, but not hair cells. Ten weeks after the procedure, some ofthe transplanted cells had grown projections that formed connections to the brain stem. Subsequent testing showed that many of the animals could hear much fainter sounds after transplantation, with an overall improvement in hearing of 46%.

Rivoltas findings along with a study published in July showing that gene therapy can restore hearing in deaf-born mice2 reinforce a spate of studies demonstrating that stem cells and gene therapy can restore sensory functions, including smell (see 'Gene therapy restores sense of smell to mice') and vision (see 'Regenerative medicine repairs mice from top to toe').

The advances are exciting, says John Brigande, a developmental biologist at Oregon Health & Science University in Portland who has a progressive form of hearing loss and is exploring stem-cell-based approaches to restore auditory function. He notes, however, that because the exquisite architecture of the inner ear can be damaged in many different ways, there wont be one cure for hearing loss, there will be a variety of interventions tailored to unique conditions.

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Human embryonic stem cells restore gerbil hearing

The demonstration in rodents could one day be combined with cochlear implants to treat more people than is currently possible.

Sound effects: Human stem-cell-derived neurons repopulate the inner ear of deaf gerbils. Human cells are labeled green, red, and yellow, where red and yellow mark mature or maturing neurons. Marcelo Rivolta, University of Sheffield

Researchers have restored hearing in deaf rodents using human embryonic stem cells, demonstrating for the first time that these cells can replace missing or damaged neurons in the auditory pathway. The authors suggest that this method could one day be used in combination with cochlear implants. Such an approach would aid more deaf patients than can currently benefit from the bionic prosthetic alone.

Cochlear implants can help patients who have lost or damaged hair cellsthe first sensory cells in the auditory pathwaybut don't work if patients have also lost the neurons that transmit the auditory information to the brain. By filling in this part of the auditory pathway, the new approach could enable doctors to use cochlear implants to treat even those patients who have lost both their hair cells and the signal-transmitting neurons.

Patients can lose these neurons if their hair cells are no longer working or are missing. "Most causes of hearing losswhether it is congenital hearing loss from some sort of genetic defect or acquired hearing loss from chronic noise exposure or powerful antibiotics or chemotherapygenerally those patients have a hair-cell-based hearing loss," says Daniel Lee, a surgeon at the Massachusetts Eye and Ear Infirmary in Boston who performs cochlear implantations. "Over time, after you lose the ability to hear due to hair-cell loss, the neurons get pruned back due to lack of activity," he says.

To address the loss of these cells, Marcelo Rivolta, a sensory-stem-cell biologist at the University of Sheffield in England, and his coauthors devised a method to turn human embryonic stem cells into ear-cell progenitors, cells that can then be transplanted into the inner ear, where they further differentiate into auditory neurons.

The researchers demonstrated that the transplanted cells could transmit sound signals into the brain. They did this by measuring the electrical activity of the neurons in response to sound. While other groups had previously shown that mouse embryonic stem cells can differentiate into these auditory neurons and grow within the inner ear after transplantation, they were unable to demonstrate a functional recovery.

The ultimate goal of stem-cell therapy is to replace both the hair cells and the neurons, says Rivolta, but the procedure is much more difficult for the hair cells. "We are still lacking a surgical technique to deliver the cells in the right place without damaging the ear. Moreover, the cells would need to graft in a perfect arrangement, at a correct angle," he says.

The stem-cell treatment could eventually be combined with cochlear implants to give more deaf patients the ability to hear. But much more work would be required to bring this idea to fruition.

While the study shows the potential of stem cells to replace auditory nerve fibers, says Stefan Heller, who studies hair-cell function and regeneration at the Stanford School of Medicine, the results will be difficult to translate to patients. "It is virtually impossible to diagnose a reduction of auditory nerve fibers in hearing-loss patients." The risk of tumor formation, an issue carried by all potential embryonic stem-cell therapies, are also carried by this treatment, he says.

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Researchers Use Human Embryonic Stem Cells to Restore Hearing

September 12, 2012 in Health

Malcolm Ritter Associated Press

Marcelo Rivolta photo

This undated photo provided by Nature shows cells in the inner ear of a deaf gerbil. The yellow ones are nerve cells derived from human embryonic cells. These cells improved the hearing of the gerbils, in an experiment that may someday help human patients. Results of the work, done in gerbils, were reported online Wednesday, Sept. 12, 2012 in the journal Nature by a team led by Dr. Marcelo Rivolta of the University of Sheffield inEngland. (Full-size photo)

NEW YORK (AP) For the first time, scientists have improved hearing in deaf animals by using human embryonic stem cells, an encouraging step for someday treating people with certain hearingdisorders.

Its a dynamite study (and) a significant leap forward, said one expert familiar with the work, Dr. Lawrence Lustig of the University of California, SanFrancisco.

The experiment involved an uncommon form of deafness, one that affects fewer than 1 percent to perhaps 15 percent of hearing-impaired people. And the treatment wouldnt necessarily apply to all cases of that disorder. Scientists hope the approach can be expanded to help with more common forms of deafness. But in any case, it will be years before human patients mightbenefit.

Results of the work, done in gerbils, were reported online Wednesday in the journal Nature by a team led by Dr. Marcelo Rivolta of the University of Sheffield inEngland.

To make the gerbils deaf in one ear, scientists killed nerve cells that transmit information from the ear to the brain. The experiment was aimed at replacing thosecells.

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Human stem cells restore hearing in gerbil study - Wed, 12 Sep 2012 PST

NEW YORK

For the first time, scientists have improved hearing in deaf animals by using human embryonic stem cells, an encouraging step for someday treating people with certain hearing disorders.

"It's a dynamite study (and) a significant leap forward," said one expert familiar with the work, Dr. Lawrence Lustig of the University of California, San Francisco.

The experiment involved an uncommon form of deafness, one that affects fewer than 1 percent to perhaps 15 percent of hearing-impaired people. And the treatment wouldn't necessarily apply to all cases of that disorder. Scientists hope the approach can be expanded to help with more common forms of deafness. But in any case, it will be years before human patients might benefit.

Results of the work, done in gerbils, were reported online Wednesday in the journal Nature by a team led by Dr. Marcelo Rivolta of the University of Sheffield in England.

To make the gerbils deaf in one ear, scientists killed nerve cells that transmit information from the ear to the brain. The experiment was aimed at replacing those cells.

Human embryonic stem cells can be manipulated to produce any type of cell. Using them is controversial because they are initially obtained by destroying embryos. Once recovered, stem cells can be grown and maintained in a lab and the experiment used cells from lab cultures.

The stem cells were used to make immature nerve cells. Those were then transplanted into the deaf ears of 18 gerbils.

Ten weeks later, the rodents' hearing ability had improved by an average of 46 percent, with recovery ranging from modest to almost complete, the researchers reported.

And how did they know the gerbils could hear in their deafened ears? They measured hearing ability by recording the response of the brain stem to sound.

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Human stem cells restore hearing in gerbil study

Eighteen gerbils were given a drug to make them deaf in one ear, before being given an injection of 50,000 progenitor cells into the cochlea, which translates sounds into nerve impulses which can be sent to the brain.

On average about a third of the cells grafted themselves to the ear and replace the damaged nerve cells. Brain scans showed that the gerbils typically recovered 45 per cent of their hearing after 10 weeks.

In humans this would translate to someone who could formerly not hear a lorry passing by their window gaining the ability to follow a conversation in a crowded room, researchers said.

They added that the results were variable, with some gerbils recovering up to 90 per cent of their hearing and others seeing very little improvement, depending on how many of the cells took hold.

More research is needed to establish that the benefits of the treatment are lasting and that it is safe for use on humans, but the study represents a "huge step forward" in deafness research, the team said.

Dr Marcelo Rivolta, who led the study, said: "Stem cells have been used in animal models of deafness before, mostly the mouse, with different results, but none have shown functional recovery. What we have shown here is functional recovery using human stem cells, which is unique.

"It is difficult to say when we might be able to treat patients. We are hoping in a few years, but first we need to understand more about the biology of the system and whether it is sustainable in time and safe."

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Stem cells restore hearing to deaf gerbils

ScienceDaily (Sep. 11, 2012) A novel set of custom-designed "molecular beacons" allows scientists to monitor gene expression in living populations of stem cells as they turn into a specific tissue in real-time. The technology, which Brown University researchers describe in a new study, provides tissue engineers with a potentially powerful tool to discover what it may take to make stem cells transform into desired tissue cells more often and more quickly. That's a key goal in improving regenerative medicine treatments.

"We're not the inventors of molecular beacons but we have used it in a way that hasn't been done before, which is to do this in long-term culture and watch the same population change in a reliable and harmless way," said graduate student Hetal Desai, lead author of the paper published online Sept. 5, 2012, in the journal Tissue Engineering Part A.

In their research, Desai and corresponding author Eric Darling, assistant professor of biology in the Department of Molecular Pharmacology, Physiology, and Biotechnology, designed their beacons to fluoresce when they bind to mRNA from three specific genes in fat-derived stem cells that are expressed only when the stem cells are transforming into bone cells.

Throughout 21 days of their development, the cells in the experiments remained alive and unfettered, Desai said, except that some populations received a chemical inducement toward becoming bone and others did not. Over those three weeks, the team watched the populations for the fluorescence of the beacons to see how many stem cells within each population were becoming bone and the timing of each gene expression milestone.

The beacons' fluorescence made it easy to see a distinct pattern in that timing. Expression of the gene ALPL peaked first in more than 90 percent of induced stem cells on day four, followed by about 85 percent expressing the gene COL1A1 on day 14. The last few days of the experiments saw an unmistakably sharp rise in expression of the gene BGLAP in more than 80 percent of the induced stem cells.

Each successive episode of gene expression ramped up from zero to the peak more quickly, the researchers noted, leading to a new hypothesis that the pace of the stem cell transformation, or "differentiation" in stem cell parlance, may become more synchronized in a population over time.

"If you could find a way to get them on this track earlier, you could get the differentiation faster," Darling said.

Meanwhile the stem cell populations that were not induced with bone-promoting chemicals, showed virtually no beacon fluorescence or expression of the genes, indicating that the beacons were truly indicators of steps along the transformation from stem cell to bone.

Beacons don't affect cells

Desai said the team took extra care to design beacons that would not alter the cells' development or functioning in any way. While the beacons do bind to messenger RNA produced in gene expression, for example, they do not require adding any genes to the stem cells' DNA, or expressing any special proteins, as many other fluorescence techniques do.

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Molecular beacons light up stem cell transformation

Public release date: 10-Sep-2012 [ | E-mail | Share ]

Contact: Bill Seiler bseiler@umm.edu 410-328-8919 University of Maryland Medical Center

Baltimore, MD September 10, 2012 Researchers at the University of Maryland School of Medicine, who are exploring novel ways to treat serious heart problems in children, have conducted the first direct comparison of the regenerative abilities of neonatal and adult-derived human cardiac stem cells. Among their findings: cardiac stem cells (CSCs) from newborns have a three-fold ability to restore heart function to nearly normal levels compared with adult CSCs. Further, in animal models of heart attack, hearts treated with neonatal stem cells pumped stronger than those given adult cells. The study is published in the September 11, 2012, issue of Circulation.

"The surprising finding is that the cells from neonates are extremely regenerative and perform better than adult stem cells," says the study's senor author, Sunjay Kaushal, M.D., Ph.D., associate professor of surgery at the University of Maryland School of Medicine and director, pediatric cardiac surgery at the University of Maryland Medical Center. "We are extremely excited and hopeful that this new cell-based therapy can play an important role in the treatment of children with congenital heart disease, many of whom don't have other options."

Dr. Kaushal envisions cellular therapy as either a stand-alone therapy for children with heart failure or an adjunct to medical and surgical treatments. While surgery can provide structural relief for some patients with congenital heart disease and medicine can boost heart function up to two percent, he says cellular therapy may improve heart function even more dramatically. "We're looking at this type of therapy to improve heart function in children by 10, 12, or 15 percent. This will be a quantum leap in heart function improvement."

Heart failure in children, as in adults, has been on the rise in the past decade and the prognosis for patients hospitalized with heart failure remains poor. In contrast to adults, Dr. Kaushal says heart failure in children is typically the result of a constellation of problems: reduced cardiac blood flow; weakening and enlargement of the heart; and various congenital malformations. Recent research has shown that several types of cardiac stem cells can help the heart repair itself, essentially reversing the theory that a broken heart cannot be mended.

Stem cells are unspecialized cells that can become tissue- or organ-specific cells with a particular function. In a process called differentiation, cardiac stem cells may develop into rhythmically contracting muscle cells, smooth muscle cells or endothelial cells. Stem cells in the heart may also secrete growth factors conducive to forming heart muscle and keeping the muscle from dying.

To conduct the study, researchers obtained a small amount of heart tissue during normal cardiac surgery from 43 neonates and 13 adults. The cells were expanded in a growth medium yielding millions of cells. The researchers developed a consistent way to isolate and grow neonatal stem cells from as little as 20 milligrams of heart tissue. Adult and neonate stem cell activity was observed both in the laboratory and in animal models. In addition, the animal models were compared to controls that were not given the stem cells.

Dr. Kaushal says it is not clear why the neonatal stem cells performed so well. One explanation hinges on sheer numbers: there are many more stem cells in a baby's heart than in the adult heart. Another explanation: neonate-derived cells release more growth factors that trigger blood vessel development and/or preservation than adult cells.

"This research provides an important link in our quest to understand how stem cells function and how they can best be applied to cure disease and correct medical deficiencies," says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs, University of Maryland; the John Z. and Akiko K. Bowers Distinguished Professor; and dean, University of Maryland School of Medicine. "Sometimes simple science is the best science. In this case, a basic, comparative study has revealed in stark terms the powerful regenerative qualities of neonatal cardiac stem cells, heretofore unknown."

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University of Maryland study: Neonatal heart stem cells may help mend kids' broken hearts

Injections of stem cells taken from patients blood may finally banish wrinkles if clinical trials of a new treatment are successful.

For some, wrinkles are seen as a sign of character. For most, they are an unwelcome reminder of ageing.

However, scientists are developing a method that may finally end the need for the routine of treatments and moisturisers used to try to keep facial lines at bay.

The first clinical trials are to begin shortly on a treatment that uses stem cells purified from a patients blood to combat their own wrinkles.

The cells will be injected beneath the skin where they will grow into new skin cells to help restore the elasticity, claims Pharmacells, the Glasgow-based company behind the technology.

Athol Haas, the companys chief executive, said: The skin has a natural elastic property which comes from cells known as fibroblasts.

The ability of the body to produce this elastic material slows down with age because the number of these fibroblasts decrease.

By introducing large numbers of stem cells into the right place, we are increasing the ability of the body to produce this material. It is still in its early stages but we hope to begin phase one trials within the next 12 months.

Until recently, anyone hoping to get rid of their wrinkles had to rely on cosmetic treatments that injected synthetic collagen under the skin as a filler to remove the lines.

Botox has now become popular for cosmetic treatments, where a neurotoxin from the bacteria Clostridium botulinum is injected to immobilise the muscles that can cause wrinkles.

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Stem Cells Could Be The Next Anti-Aging Fad

Public release date: 11-Sep-2012 [ | E-mail | Share ]

Contact: Phyllis Fisher phyllis.fisher@gmail.com 212-606-1724 Hospital for Special Surgery

Researchers at Hospital for Special Surgery have been awarded a $100,000 grant from the National Football League (NFL) Charities to research the use of platelet-rich plasma (PRP) and stem cells as treatments for tendon injury and degeneration. For years, PRP has been used to improve healing in various sports injuries, but there is little evidence of its efficacy. Tendon overuse injuries are commonly seen in NFL players and recreational athletes, and new treatments are needed.

"We don't have a treatment that works 100 percent of the time, so there is room for improvement," said Scott Rodeo, M.D., co-chief of the Sports Medicine and Shoulder Service for Hospital for Special Surgery in New York City. "Many people are weekend warriors and they suffer from tendon overuse injuries. Hopefully, our study will be able to help a lot of these people." Dr. Rodeo will be heading up the research. He has been associate team physician for the New York Football Giants since 2000.

The results of the research could lead to the development of an effective therapeutic strategy for tendinopathy that may allow NFL players to return to competition more quickly. It may also lead to a decrease in complications related to tendinosis, such as tendon ruptures.

Tendinosis is caused by repetitive microtears in the connective tissue in and around the tendon along with a failure of the body to mount a full healing response. Over time it can lead to pain, reduced tensile strength and chance of tendon rupture.

The grant money will be used to investigate how degenerated tendons respond to PRP and bone marrow-derived stem cells as well as if these two treatments will be synergistic if they are combined. Researchers will test these treatments in a preclinical model of tendon injury and degeneration. Among the goals of the research are to examine the structural and mechanical properties of the treated tendon tissue and to see how it responds to PRP and stem cells.

In recent years, physicians have found that some, but not all, patients with tendon disorders respond to treatment with PRP. PRP contains cells and growth factors that may stimulate healing of bone and soft tissue. Researchers surmise the mixed results may be caused by variations in preparation, timing, dosage and delivery of platelets, or differences in bioactivity. Different PRP preparations contain different amounts of cell and growth factors, and the researchers speculate that the negative studies may have used PRP preparations with low bioactivity. To test this theory, researchers will test the bioactivity levels of the preparations used. It is also unclear whether PRP treatments actually help heal the tendon structure or just ameliorate the pain. An examination of tissue should provide an answer to this question.

"We don't really understand how PRP affects tendon structure after we place it into patients. Some individuals get pain relief while others do not. The reported clinical results are mixed, " said Richard Ma, M.D., an orthopedic surgery fellow in the Sports Medicine and Shoulder Service at Hospital for Special Surgery and co-principal investigator for the study. "The advantage of a preclinical research model is we can not only evaluate the effects of PRP on tendon architecture after injury, but we can also evaluate how it might improve the structural strength of these tendons.

Similar to PRP, studies using stem cells to treat tendon disorders have also yielded conflicting results. HSS researchers hope their experiments can tease out how this treatment impacts tendons. "Cell therapies such as bone marrow stem cells are attractive because it may provide the necessary stimulus to overcome the unfavorable biologic microenvironment in chronic tendon degeneration," said Dr. Ma. Stem cells have the capability of differentiating into diverse specialized cell types.

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Hospital for Special Surgery investigators receive National Football League grant for PRP research

September 10, 2012

Brett Smith for redOrbit.com Your Universe Online

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People have always been searching for the cosmetic Fountain of Youthgrey hairs are dyed, tummies are tucked, and wrinkles are Botoxed.

According to the Scottish company Pharmacells, these modern day Ponce de Leons may have an exciting development to celebrate as the company is about to start clinical trials of a treatment that uses stem cells derived from a patients own blood to eliminate wrinkles.

The skin has a natural elastic property which comes from cells known as fibroblasts, Athol Haas, the companys chief executive, told the Telegraphs Richard Gray.

The ability of the body to produce this elastic material slows down with age because the number of these fibroblasts decreases, he said. By introducing large numbers of stem cells into the right place, we are increasing the ability of the body to produce this natural material. It will be long lasting, we think at least five years if not longer.

Commercially using stem cells for skin care is actually being done today. However, the stem cells are derived from a sample of the patients fat cells, not their blood. According to Haas, his companys treatment is superior to those that use fat-derived stem cells.

The stem cells in fat are more mature so the quality is not so good, and the numbers of them in it are much smaller, around five or 10 million, Haas explained. We are talking about 500 million, very high quality, pure stem cells and there is definitely a link between dose and efficacy. The more you have, the better it should be.

These pure stem cells and their potential applications were first discovered by American researchers about 10 years ago, and are currently used in hospitals to treat organs in the event of a trauma.

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Fountain Of Youth Found? Stem Cells Eliminate Wrinkles