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AMNIOTIC STEM CELLS HEAL INTESTINAL DISORDER

In STEM CELLS IN THE NEWS on March 27, 2013 at 9:00 am

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Amniotic stem cells heal intestinal disorder that afflicts premature babies

A new study published in GUT (An International Journal of Gastroenterology and Hepatology) has shown that amniotic fluid stem cells can reverse intestinal damage in rats caused by necrotising enterocolitis — an often fatal disorder that afflicts premature babies.

Paolo De Coppi had already proved that amniotic fluid could be reprogrammed in a similar way to how we reprogram embryonic stem cells, and without introducing potentially damaging genes to instigate the transformation (how adult cells are made pluripotent). Though not quite as versatile as the embryonic version, De Coppi showed that they could be converted into liver, bone and nerve cells.

What’s interesting about this latest study is that the stem cells calmed the intestinal inflammation, healed and reversed damage done to the gut far better than bone marrow stem cells (used in a rate control group), and in an unexpected way. After being injected, the cells travelled to the tiny villi that line the intestinal walls and absorb nutrients, where it then released an unknown substance that triggered progenitor cells to calm the inflammation and instigate tissue and villi regrowth. The team is unsure exactly how it released a growth factor to kick the progenitor cells into action, but it’s hoping further studies could clear this up — that knowledge could then be used to develop drugs that replicate the same action.

In the meantime, De Coppi says, “we hope that stem cells found in amniotic fluid will be used more widely in therapies and in research, particularly for the treatment of congenital malformations”.

Necrotising enterocolitis is common in premature babies, with inflammation rapidly leading to tissue death and a perforated intestine if antibiotics have no effect. At that point, an operation is the only option and these have a 70 percent survival rate due to related risks of surgery at such a young age, and can leave infants with a shortened intestine and trouble eating for the rest of their lives. This latest study gives hope for an injectable, non-invasive solution.

Stem cells have already been shown to have some incredible properties for regenerative medicine — most recently baboon embryonic stem cells were used to repair damaged arteries. However, due the ethical grey area embryonic experiments reside in, progress has inevitably been slower, with the first official human trials only recently beginning to take place. Stem cells derived from amniotic fluid have huge potential, but would mainly still rely on donors given the impracticalities of storing fluid from every birth. Nevertheless, according to estimates published in a 2005 study, just 150 donors would provide a match for 38 percent of the population.

De Coppi, who in 2010 made headlines when he built an 11-year-old boy a trachea replacement from his own bone marrow stem cells, is currently raising funding for his research into building rejection-free transplants from stem cells.

http://www.wired.co.uk/news/archive/2013-03/25/amniotic-fluid

Image: Shutterstock

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SCIENCE FICTION COMES ALIVE WITH ORGANS GROWN IN A LAB

In SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on March 26, 2013 at 9:00 am

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Building a complex human organ in the lab is no longer a dream of science fiction. At London’s Royal Free Hospital, a team of 30 scientists is manufacturing a variety of body parts, including windpipes, noses and ears. WSJ’s Gautam Naik reports. Photo: Gareth Phillips

Science Fiction Comes Alive as Researchers Grow Organs in Lab

MADRID—Reaching into a stainless steel tray, Francisco Fernandez-Aviles lifted up a gray, rubbery mass the size of a fat fist.  It was a human cadaver heart that had been bathed in industrial detergents until its original cells had been washed away and all that was left was what scientists call the scaffold.  Next, said Dr. Aviles, “We need to make the heart come alive.”

Inside a warren of rooms buried in the basement of Gregorio Marañón hospital here, Dr. Aviles and his team are at the sharpest edge of the bioengineering revolution that has turned the science-fiction dream of building replacement parts for the human body into a reality.  Since a laboratory in North Carolina made a bladder in 1996, scientists have built increasingly more complex organs. There have been five windpipe replacements so far. A London researcher, Alex Seifalian, has transplanted lab-grown tear ducts and an artery into patients. He has made an artificial nose he expects to transplant later this year in a man who lost his nose to skin cancer.

“The work has been extraordinarily pioneering,” said Sir Roy Calne, an 82-year-old British surgeon who figured out in the 1950s how to use drugs to prevent the body from rejecting transplanted organs.

Now, with the quest to build a heart, researchers are tackling the most complex organ yet. The payoff could be huge, both medically and financially, because so many people around the world are afflicted with heart disease. Researchers see a multi billion dollar market developing for heart parts that could repair diseased hearts and clogged arteries.

In additional to the artificial nose, Dr. Seifalian is making cardiovascular body parts. He sees a time when scientists would grow the structures needed for artery bypass procedures instead of taking a vein from another part the body. As part of a clinical trial, Dr. Seifalian plans to transplant a bio-engineered coronary artery into a person later this year. His employer, University College London, has designated a person to oversee any future commercialization of it and other man-made organs.

The development of lab-built body parts is being spurred by a shortage of organ donors amid rising demand for transplants. Also, unlike patients getting transplants, recipients of lab-built organs won’t have to take powerful anti-rejection drugs for the rest of their lives. That’s because the bio-engineered organs are built with the patients’ own cells.

Until the late 1980s, few scientists believed it would be possible to make human organs because it was a struggle to grow human cells in the laboratory. The task became easier once scientists figured out the chemicals—known as growth factors—that the body itself uses to promote cellular growth.

Scientists started out growing simple organs. In 1999, Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in Winston-Salem, N.C., implanted lab-grown bladders into the first of several children with severely dysfunctional bladders. The organs have continued to function well for several years. Dr. Atala’s team now is trying to grow a whole range of bio-engineered parts, from simple blood vessels to human livers.

Some of the most complex work is under way at Dr. Seifalian’s laboratory.   A 56-year-old native of Iran, Dr. Seifalian started out as a nuclear physicist, and became interested in medical uses of nuclear technology. That ultimately led him to bioengineering.  In 2011, Dr. Seifalian made a windpipe from a patient’s cells. It was used to replace the cancerous windpipe of the patient, saving his life, his surgeon has said.

Dr. Seifalian and 30 scientists now seek to build a larynx, ears, noses, urethras and bile ducts  Most human organs get their form from an internal scaffolding of collagen and other proteins. Scientists struggled for years to find a replacement material that was strong and flexible and yet wouldn’t be rejected by the bodyEventually, they homed in on a couple of high-tech materials made from plant fibers, resins and other substances. Dr. Seifalian said he uses a material that is modeled on the honeycomb structure of a butterfly’s wing. The material, a so-called nanocomposite, is resistant to infectious bacteria and has pores that are the right size to hold cells.  “The material has to be accepted by the body, but it also has to be easy to manipulate into different shapes, different strengths,” said Dr. Seifalian.

The nose in the jar was closely modeled on the nose of a 53-year-old Briton. With the help of imaging scans and a glass mold designed by an artist, researchers first fabricated a replica of the original nose. The patient was asked if he wanted a slight deviation in his septum to be straightened out, but he turned down the offer, according to Dr. Seifalian.  The researchers poured the material into the artist’s mold. They added salt and sugar. That created holes in the material and gave it a spongy, porous feel, just like the real thing.  The key to all the lab-built organs are stem cells, found in human bone marrow, fat and elsewhere. Stem cells can be transformed into other tissues of the body, making them the basic building blocks for any organ.

In the case of the nose, stem cells extracted from the patient’s fat tissue were added to the artist’s mold, along with chemicals that control cell development. The stem cells sat inside the pores of the lab-made organ and gradually differentiated into cells that make cartilage.  However, the nose was missing a crucial piece: skin.  This posed a substantial hurdle. No one has made natural human skin from scratch. Dr. Seifalian’s idea: to implant the nose under the skin of the patient’s forehead in the hope that skin tissue there would automatically sheath the nose.

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But the patient objected, and for good reason: The implanted nose would have to sit inside his forehead for weeks or even months. In the end, Dr. Seifalian chose a less obtrusive approach. The bio-engineered nose was implanted under the patient’s forearm.  The team now is using imaging equipment to keep tabs on whether the necessary blood vessels, skin and cartilage are forming in the right way. “We’ll have to also make sure there’s no infection,” Dr. Seifalian said in late November, on the day of the patient’s surgery.  If the skin graft works, surgeons will remove the nose from the arm and attach it to the patient’s face. Dr. Seifalian will then apply the right chemicals to convert the man’s stem cells into epithelial cells, a common type of tissue found in the nose and in the lining of other organs. The epithelial cells will be inserted into the nose.  As a final step, surgeons will connect blood vessels from the face to the site of the new nose to provide a steady flow of nourishment for the growing cells. “The whole process could take six months,” said Dr. Seifalian. He estimates the cost of making the nose in the lab is about $40,000, but the patient isn’t being charged because the doctors and scientists are either donating their time or working on this as part of their research.

Dr. Seifalian said the new nose could restore some sense of smell to the patient, but its main benefit will be cosmetic. He held up a jar full of early-stage lab-made noses, and another filled with early-stage ears.

“We’re actually in the process of making a synthetic face,” he said. From a cosmetic point of view, “if you can make the ear and the nose, there’s not much left.”  Regenerating a nose would be a striking achievement; creating a complex organ like the heart would be historic. A team led by Spain’s Dr. Aviles is trying to get there first.

Dr. Aviles trained as a cardiologist but became frustrated with the difficulty of treating patients with advanced heart disease. The only option for the worst cases was a heart transplant, and there was a shortage of hearts. Spain has the highest donor rate in the world, yet Dr. Aviles said that only about 10% of patients who need a heart transplant get one.

He was approached in 2009 by a U.S. scientist, Doris Taylor, who had already grown a beating rat heart in the lab while at the University of Minnesota. Instead of using a man-made scaffold, Dr. Taylor had used the scaffolding from an actual rat heart as the starting point. She believed the same technique was crucial for making a working human heart. She was attracted to Spain because the higher donor rate meant that more hearts unsuitable for transplant could be used for experiments.

Dr. Aviles and about 10 colleagues began their human-heart experiments crammed into a small storage room at the hospital. In 2010, a sparkling new lab opened. It has two large freezers with human cells and human hearts, and a dozen stainless steel sinks containing pig hearts immersed in a colorless liquid.  Growing a heart is much harder than, say, growing a windpipe, because the heart is so big and has several types of cells, including those that beat, those that form blood vessels, and those that help conduct electrical signals. For a long time, scientists didn’t know how to make all the cells grow in the right place and in the right order.

The problem had been cracked by Dr. Taylor. She said that when human stem cells were put into a heart scaffold in 2010, they seemed to know just where to go. “They organized themselves in a way I didn’t believe,” said Dr. Taylor, who now works at the Texas Heart Institute but makes regular visits to Madrid to help with the experiments. “It’s amazing that the [scaffold] can be as instructional as it is. Maybe we don’t need to micromanage every aspect of this.”

Dr. Aviles said he hopes to have a working, lab-made version ready in five or six years, but the regulatory and safety hurdles for putting such an organ in a patient will be high. The most realistic scenario, he said, is that “in about 10 years” his lab will be transplanting heart parts.

He and his team already have grown early-stage valves and patches that could be used some day to repair tissue damaged by heart attack..  The Madrid lab has made only baby steps toward its grand plan to grow a human heart using the same techniques that Dr. Taylor pioneered with a rat heart.

“We opened the door and showed it was possible,” she said. “This is no longer science-fiction. It’s becoming science.”

A version of this article appeared March 22, 2013, on page A1 in the U.S. edition of The Wall Street Journal, with the headline: Science Fiction Comes Alive As Researchers Grow Organs in Lab.

STEM CELL THERAPY INCREASES SUCCESS RATE OF LIVER TRANSPLANTS

In ALL ARTICLES, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on March 20, 2013 at 9:00 am

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Stem cell therapy is new hope for liver transplant patients

Stem cell therapy has been found useful in over 60 per cent of the patients due for liver transplant, as per a paper submitted by doctors at Sir Ganga Ram Hospital in Delhi recently. Not only is the treatment less cumbersome and risky, its cost is also comparatively very reasonable.

According to the paper’s principal author and chairman of the Department of Gastroenterology and Liver Diseases at the Hospital, Dr. Anil Arora, a large number of patients requiring liver transplantation cannot afford it for two reasons – cost and donor availability.

In view of the logistical problems faced by such patients, Dr. Arora said: “We started looking at the feasibility of alternative methods like using reserve cells in the body for such treatment, as it costs even less.  Some of these cells can be mobilized from the bone marrow as it has the capacity to regenerate the cells. So we stimulate the bone marrow by an injection.”

“This injection is given for five days and it mobilizes the bone marrow and some of the cells. They then come into the blood circulation. In the study we tried to filter these cells from the blood marrow using a specialized filtering machine and the concentrate of these cells. About 5 ml to 10 ml of the blood containing these concentrated group of cells were then injected into the hepatic artery, which supplies blood to the liver,” explained Dr. Arora. He said this process was carried out by a number of different mechanisms and it proved quite successful. “We started about two years ago and finished last year. Then these patients were followed up for another one year and we were happy to see a significant proportion of the patients having substantial improvement in the liver functions as assessed by a score called ‘Child score’.”

Dr. Arora said, “All patients tolerated the treatment well without any side effects. Of the 10 patients, six to seven benefited. So we believe that more frequent administration of the stem cells in large number might have a more beneficial impact.”

While the study by the Sir Ganga Ram Hospital team was published this year and was approved by the Department of Biotechnology and Ministry of Science and Technology, Government of India, Dr. Arora said there is also other published data now which calls for “stimulating the bone marrow and letting the cells automatically go into the liver”. By this, he said, you avoid filtering and putting the blood with the stem cells into the liver. “This is also equally beneficial.”

Dr. Arora said stem cell therapy “might act as a bridge for liver transplant” and can provide some time to the patients to arrange for treatment. But just like a damaged car tire, he said, a damaged liver after minor repairs has to be replaced. “However, if a person stops taking liquor or if the therapy goes on well, then a patient can lead a healthy life for many more years.”

http://www.thehindu.com

Parkinson’s patients fund their own stem cell research

In BUSINESS OF STEM CELLS, SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on March 19, 2013 at 9:00 am

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Healing Parkinson’s patients with their own stem cells

Up to 1 million Americans have Parkinson’s, according to the Parkinson’s Disease Foundation. Because aging is the chief risk factor for the disease, the patient population is expected to increase as the baby boom generation gets older.  Parkinson’s selectively kills brain cells that make the neurotransmitter dopamine, which enables movement. No one knows how it happens, or how to stop it. Researchers expect that transplanted dopamine-producing brain cells will eventually die, but perhaps not for 10 to 15 years.

The most visible symptoms of Parkinson’s include tremors, slowed movement, stooped posture and loss of balance, and trouble speaking. People sometimes walk with a shuffling gait, and they may experience severe and chronic pain. Patients’ faces can assume a mask-like expression.  Drugs that provide dopamine or mimic its effects can partially relieve the symptoms, but they produce side effects such as uncontrolled movement. Also, their effectiveness decreases over time.

A groundbreaking stem cell treatment for Parkinson’s disease is getting close to moving from lab research in La Jolla to therapy for patients. The research, funded by the patients and their supporters, could also pioneer a new model for moving medical advances from the lab into the clinic.

Eight Parkinson’s patients have allied with scientists from The Scripps Research Institute and medical professionals from Scripps Clinic for the project, which involves creating new brain cells from other cells in their own bodies. Because of the unusual, personalized nature of the research, the patients are participating with scientists and doctors as equals, meeting regularly to review the progress.

The ambitious goal is to relieve the movement difficulties Parkinson’s causes by replacing the brain cells the disease destroys. In theory, it would restore near-normal movement for a decade or more, and the procedure could be repeated as needed.

Research is far enough along that scientists and health care professionals in the project are talking to regulators about beginning clinical trials, perhaps as soon as next year.

The replacement brain cells are now being grown in a lab at The Scripps Research Institute. Patches of skin the diameter of a pencil eraser were removed from the patients’ arms and turned into a new kind of stem cell that acts like embryonic stem cells. Called induced pluripotent stem cells, they were discovered in 2006, a feat honored by a Nobel Prize last year.

These IPS cells can become nearly any kind of cell in the body… Another potential advantage of IPS cells over embryonic stem cells is that they should be less prone to rejection by the patients’ immune systems, because the transplanted cells come from the individuals themselves.

Patient Cassandra Peters, 57, learned of the reality of Parkinson’s and the hope of a new treatment in a visit with Dr. Houser, her neurologist.  “Interestingly, when I first had a conversation with her, when she definitively told me I had Parkinson’s, she said to me, quote, “You will have a stem cell procedure in your lifetime.”  I took that ball and held it in my heart, thinking, this is going to be my ‘get out of jail free’ card.  Not a day goes by when I don’t have an opportunity to share what I’m going through now and what the future might hold,” Peters said.

Ileana Slavin, a research associate in the lab of Jeanne Loring, and Suzanne Peterson, a staff scientist, discuss what it means for scientists to directly meet the people they’re trying to help.  Diabetes researcher Matthias von Herrath of the La Jolla Institute for Allergy & Immunology said the work could help scientists developing stem cell therapies for diabetics,” von Herrath said. “And that’s going to open the door for these type of stem cells.”

Loring’s researchers are reaching the final stages of their part of the project. They have made induced pluripotent stem cells from all eight patients, and have turned those into the needed brain cells for two of them. The work continues for the other six.

Parkinson’s represents the “low-hanging fruit” of neurological diseases for stem cell therapy.  We know what cell types are lost in Parkinson’s disease,” Bratt-Leal said in a March 8 meeting of the group. “We can make them from stem cells.  And now we can make stem cells from adult tissues.  The next logical step is to make these cells from people and put them back into them.”

“With IPS cells grown from the patient, rejection should be less of a worry”, Bratt-Leal said.

Now that the research side of the project has overcome its greatest hurdles, the focus is shifting to medicine, Loring said. The replacement brain cells will be grown in a clinical grade facility at the City of Hope in Los Angeles.  As part of the transition to the medical side, Houser will provide expertise in setting up the clinical trial, assuming approval is granted by the U.S. Food and Drug Administration.

Beyond the potential benefit to the eight patients, the project may provide an answer to what Loring and other researchers call the “Valley of Death,” the period that halts promising research before it can become a medical treatment.  Most scientific research is federally funded, but commercialization is left to the private sector. If companies don’t see a way to make money, they won’t pursue a therapy, even if it works.  This problem is especially forbidding for treatments customized to individual patients. These don’t produce economies of scale, and hence are not attractive to pharmaceutical companies.  Advocates of the customized Parkinson’s therapy said it will pay off in the long run. Patients will require less medical care, and find it easier to maintain their jobs.

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DIABETIC WOUNDS TREATED WITH STEM CELLS

In ALL ARTICLES, STEM CELLS IN THE NEWS on March 16, 2013 at 9:00 am

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Pre-Clinical Research Shows Promising Treatment for Diabetic Wounds Using Stem Cells

Pre-clinical research has generated some very promising findings using adult stem cells for the treatment of diabetic wounds. The research carried out by scientists at the National University of Ireland Galway, is published in Diabetes, the official journal of the American Diabetes Association.

The work showed that a particular type of stem cell, known as the mesenchymal stem cell (MSC), could increase wound healing when applied together with a biomaterial made from collagen. Diabetic patients have an impaired ability to heal wounds and there is a critical need to develop new treatments to improve healing particularly in patients with foot ulcers. In fact, foot ulceration will affect up to 25% of people suffering from diabetes during their lives and may result in amputation.

For the past number of years, lead-author on the research paper Dr Aonghus O’Loughlin has been funded by Molecular Medicine Ireland to work in the Regenerative Medicine Institute (REMEDI) at National University of Ireland Galway and Galway University Hospitals. He collaborates with Professor Timothy O’Brien, Director of REMEDI, to develop new ways to increase healing of diabetic wounds.

Professor O’Brien, principal investigator on the research project, said: “This data will now allow us proceed to apply for approval to carry out first in human studies of this therapeutic approach. We are currently preparing the regulatory submission to undertake a human clinical trial. Meanwhile, part of the funding needed to pursue the human clinical trial has been received from Diabetes Ireland.”

“MSC’s have many attractive therapeutic properties”, Professor O’Brien added. “They can be isolated from adults and are easy to grow in the laboratory. It has been shown in Galway and by other scientists that they release special factors that can help new blood vessels to grow. Increasing blood flow is a key step in wound healing.”

REMEDI is a Science Foundation Ireland-funded research centre, led by National University of Ireland Galway, with partners in University College Cork and NUI Maynooth. The research centre is a partnership between scientists, clinicians and industry and is the leading centre in the area of stem cell and regenerative medicine in Ireland. REMEDI is a part of the National University of Ireland Galway’s translational and clinical research programme with the objective of translating research discoveries into improved patient care.

Stem Cells from Human Adipose Tissue Used to Chase Migrating Cancer Cells

In ALL ARTICLES, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on March 15, 2013 at 11:21 am
Stemness of primary AMSC lines demonstrated with differentiation along three mesenchymal lineages, Adipocyte (a, d [48], g), Osteocyte (b [48], e, h), and Chondrocyte (c [48], f, i), documented via lineage specific staining with Oil Red O, Alizarin Red, and Collagen II, respectively. (Credit: Pendleton et al. Mesenchymal Stem Cells Derived from Adipose Tissue vs Bone Marrow: In Vitro Comparison of Their Tropism towards Gliomas. PLoS ONE, 2013; 8 (3): e58198 DOI: 10.1371/journal.pone.0058198)
Using Fat to Fight Brain Cancer: Stem Cells from Human Adipose Tissue Used to Chase Migrating Cancer Cells

Mar. 12, 2013 — In laboratory studies, Johns Hopkins researchers say they have found that stem cells from a patient’s own fat may have the potential to deliver new treatments directly into the brain after the surgical removal of a glioblastoma, the most common and aggressive form of brain tumor.


The investigators say so-called mesenchymal stem cells (MSCs) have an unexplained ability to seek out damaged cells, such as those involved in cancer, and may provide clinicians a new tool for accessing difficult-to-reach parts of the brain where cancer cells can hide and proliferate anew. The researchers say harvesting MSCs from fat is less invasive and less expensive than getting them from bone marrow, a more commonly studied method.

STEM CELLS USED TO RESTORE WOMEN’S FERTILITY

In SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on March 14, 2013 at 9:00 am

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Egg-producing stem cells found in human ovaries

Scientists say they have found a way to use ovarian stem cells to perhaps one day help infertile women get pregnant — or add years to a woman’s reproductive cycle.

In a study published in Nature Medicine, researchers report finding egg-producing stem cells in human ovaries. They also report being able to make some of those ovarian stem cells grow into immature eggs that may someday be useful for reproduction.  At this point, such “seed” eggs can’t be fertilized by sperm. But if scientists are able to entice them to mature and can prove they can be fertilized and grow into embryos — a feat that has been reported in mice — it would overturn a long-held scientific belief that women can’t make new eggs as they get older.

“What it does is really open a door into human reproduction that 10 years ago didn’t even exist,” says researcher Jonathan L. Tilly, PhD, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital, in Boston.

Outside experts agree. They say the findings could have profound importance for reproductive medicine and aging, allowing doctors not only to restore a woman’s fertility but also to potentially delay menopause.  “I think the significance of this work is like reporting that we found microorganisms on Mars,” says Kutluk Oktay, MD, who directs the Division of Reproductive Medicine and the Institute for Fertility Preservation at New York Medical College in Valhalla, N.Y.

“It’s a proof of principle that they could do it,” says David F. Albertini, PhD, director of the Center for Reproductive Sciences at the University of Kansas Medical Center in Kansas City, Kan.

The egg-generating stem cells the researchers were able to extract from ovaries were very rare. The researchers only came across one for every 10,000 or so ovarian cells that they counted.  But when they took those cells and implanted them back into human ovarian tissue, they divided and essentially made young eggs.

Tilly says his team stopped short of trying to make one of the eggs functional because “for a lot of reasons, as it should be,” it is illegal in the U.S. to experimentally fertilize human eggs.

“We think the evidence provided clearly indicates that this very unique, newly discovered pool of cells does exist in women,” he says.

“It’s a really exciting result,” says Evelyn Telfer, PhD, a cell biology expert at the University of Edinburgh in Scotland.  “What we’ve previously believed is that you don’t get new eggs formed during your adult life. This discovery shows that there’s the potential for them to be formed, no question about that,” Telfer says, “but it doesn’t actually show that they’re being formed under normal conditions.”

Indeed, she notes, experience would suggest otherwise. Women, after all, do lose their fertility as they age.  “There are cells there that under certain conditions have the potential to form [eggs]. That’s the really exciting part of this work. And of course they can be used. There’s a practical application,” she says.

Telfer has pioneered a technique that allows her to take immature human eggs and turn them into mature, fertilizable eggs outside the body. She has already partnered with Tilly to try to take his “seed” eggs to the next stage of development. With special government permission, she says, they may even be able to try to experimentally fertilize the eggs.

“It’s actually opening up a whole new field of research, to define these cells, to characterize these cells, and to use them in a practical way,” she says.

Tilly says that by using egg-generating stem cells to make large numbers of viable eggs, doctors might one day be able to cut the expense of in vitro fertilization (IVF), since women would no longer have to go through multiple cycles of treatment to harvest enough eggs to generate a pregnancy.

WebMD Health News

MUSCLE REPAIR THROUGH STEM CELLS

In SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on March 13, 2013 at 9:00 am

Researchers from the University of Minnesota Use Genetically Corrected Stem Cells To Repair Muscles

University of Minnesota researchers from the Lillehei Heart Institute have combined genetic engineering techniques to repair mutations in abnormal muscle cells with cellular reprogramming to generate stem cells that can repair and regenerate muscle regeneration in a mouse model for Duchenne Muscular Dystrophy (DMD). This research is a proof-of-principle experiment that determines the feasibility of combining induced pluripotent stem cell technology and genetic engineering techniques that correct mutations to treat muscular dystrophy. Experimental strategies such as these could represent a major step forward in autologous cell-based therapies for DMD. Furthermore, it might pave the way for clinical trials to test this approach in reprogrammed human pluripotent cells from muscular dystrophy patients.

University of Minnesota researchers combined three groundbreaking technologies to achieve effective muscular dystrophy therapy in a mouse model of DMD. First, researchers reprogrammed skin cells into induced pluripotent stem cells (iPSCs). iPSCs are capable of differentiating into any of the mature cell types within an adult organism. In this case, the University of Minnesota researchers generated pluripotent cells from the skin of mice that carry mutations in two genes; the dystrophin and utrophin genes. Mice with mutations in both the dystrophin and utrophin genes develop a severe case of muscular dystrophy that resembles the type of disease observed in human DMD patients. This provided a model system platform that successfully mimicked what would theoretically occur in humans.

The second technology employed is a genetic correction tool developed at the University of Minnesota. In this case, they used a transposon, which is a segment of DNA that can jump from one location to another within the genome. The specific transposon used is the “Sleeping Beauty Transposon.” The use of this transposon allowed them to transport genes into cells in a convenient manner. The Lillehei Heart Institute researchers used the Sleeping Beauty transposon to deliver a gene called “micro-utrophin” into the iPSCs made from the DMD mice.

Sleeping Beauty Transposon

Human micro-utrophin can support muscle fiber strength and prevent muscle fiber injury throughout the body. However, there is one essential difference micro-utrophin and dystrophin: dystrophin is absent in muscular dystrophy patients, but if it is introduced into the bodies of DMD patients, their immune system will initiate a devastating immune response against it. However, in those same patients, utrophin is active and functional, which makes it essentially “invisible” to the immune system. This invisibility allows the micro-utrophin to replace dystrophin build and repair muscle fibers within the body.

Utrophin

The third technology utilized is a method to produce skeletal muscle stem cells from pluripotent cells. This procedure was developed in the laboratory of Rita Perlingeiro, who is also the principal investigator of this latest study.

Perlingeiro’s technology gives pluripotent cells a short pulse of a muscle stem cell protein called Pax3, which nudges the pluripotent cells to become skeletal muscle stem cells, which can then be exponentially expanded in culture. These Pax3-induced muscle stem cells were then transplanted back into the same strain of DMD mice from which the pluripotent stem cells were originally derived.

Pax3 and 7

When combined, these platforms created muscle-generating stem cells that would not be rejected by the body’s immune system. According to Perlingeiro, the transplanted cells performed very well in the dystrophic mice, and they generated functional muscle and responded to muscle fiber injury.

“We were pleased to find the newly formed myofibers expressed the markers of the correction, including utrophin,” said Perlingeiro, a Lillehei endowed scholar within the Lillehei Heart Institute and an associate professor in the University of Minnesota Medical School. “However, a very important question following transplantation is if these corrected cells would self-renew, and produce new muscle stem cells in addition to the new muscle fibers.”

By injuring the transplanted muscle and watching it repair itself, the researchers demonstrated that the transplanted muscle stem cells endowed the recipient mice with fully functional muscle cells. This latest project provides the proof-of-principle for the feasibility of combining induced pluripotent stem cell technology and genetic correction to treat muscular dystrophy.

“Utilizing corrected induced pluripotent stem cells to target this specific genetic disease proved effective in restoring function,” said Antonio Filareto, Ph.D., a postdoctoral fellow in Perlingeiro’s laboratory and the lead author on the study. “These are very exciting times for research on muscular dystrophy therapies.”

These studies pave the way for testing this approach in a clinical trial that would use reprogrammed human pluripotent cells from muscular dystrophy patients.

According to Perlingeiro, “Developing methods to genetically repair muscular dystrophy in human cells, and demonstrating efficacy of muscle derived from these cells are critical near-term milestones, both for the field and for our laboratory. Testing in animal models is essential to developing effective technologies, but we remained focused on bringing these technologies into use in human cells and setting the stage for trials in human patients.”

This research was published in Nature Communications.

Article written by: mburatov

PLURIPOTENT CELLS DISCOVERED IN ADULT BREAST TISSUE

In STEM CELLS IN THE NEWS on March 12, 2013 at 9:00 am

epscolony

The top middle panel shows endogenous pluripotent somatic (ePS) cells, which can give rise to many tissue derivatives, including pancreas, bone, intestine, breast and cartilage cells.

“More evidence that any part of the body associated with reproduction has powerful stem cells with significant regenerative abilities!” – DG

New Type of Pluripotent Cell Discovered In Adult Breast Tissue

UC San Francisco researchers have found that certain rare cells extracted from adult breast tissue can be instructed to become different types of cells – a discovery that could have important potential for regenerative medicine.  As with human embryonic stem cells, the newly found cells are pluripotent, or capable of turning into most cell types, the authors said. The scientists discovered that when the cells were put either in mice, or in cell culture, the cells could differentiate to produce multiple cell types, including those that proceed to make heart, intestine, brain, pancreas and even cartilage.  The finding is significant, the authors said, because scientists previously believed that pluripotent cells did not exist in the body after the embryonic stage of human development.

“The ability of cells from an adult body to make so many tissue derivatives was completely unexpected,” said senior author Thea D. Tlsty, PhD, a UCSF professor of pathology. “When we saw that they could make cartilage, bone, gut, brain, pancreas cells – and even beating heart tissue – we were excited and intrigued.”

Though the newly discovered cells share some characteristics of embryonic stem cells, they appear to be unique to themselves, said Tlsty. They are mortal and genetically stable – characteristics that are barriers to subsequent cancer formation, which is a factor that could prove valuable if the cells are to be used for regenerative medicine, she explained. By contrast, human embryonic stem cells as well as engineered induced pluripotent stem cells, also known as iPS cells, are immortal and genetically unstable.

Additionally, the cells can expand to an extensive yet finite number before they stop growing. One cell can grow for almost 60 population doublings, producing in excess of one billion daughter cells, conceptually providing enough cells to help in the recovery of damaged or diseased tissue.  The scientists are currently searching for the rare cells in other organs of the body. They hypothesize that these “universal patch kits” are scattered throughout the body of adult men and women.

The special cells were discovered and isolated in healthy breast tissue from women of various ages and ethnicities who were undergoing breast reductions. All tissues used in the study were devoid of visible disease or contamination.

From Breast Tissue to Beating Heart Cells

Even a single one of these endogenous pluripotent somatic (ePS) cells, when placed in the appropriate conditions, exhibited the same pluripotent power to self-renew and to generate multiple lineages – both in vitro and in vivo – as embryonic stem cells. The cells could develop into any of the three germ layers: endoderm (such as the pancreas and gastrointestinal tract), the mesoderm (bone, heart muscle, blood vessel), or ectoderm (breast tissues and nervous system).

For example, when properly instructed, some ePS cells made human breast tissue that produced milk in transplanted mice, while other cells generated cartilage structures. To the surprise of the researchers, when the cells were differentiated into heart muscle, they even demonstrated the spontaneous beating seen in cardiomyocytes, or “beating heart” cells.

“The cells we describe here exist in the body devoid of commitment,” the authors wrote. “Taken together, these studies provide morphological, molecular and functional evidence of lineage plasticity of these cells. They will make human milk, bone, fat – they will beat like a heart.”

Only a small fraction of certain mammary cells have “this complete and sustained” unique profile capable of morphing themselves, the researchers said.

“Future research will tell us if we lose access to these cells as we age, if they are found in all tissues, and if they can be used to rescue diseased tissues,” said Tlsty.

“The observation that rare cells within an adult human body have the capacity to differentiate into many tissue types under different physiological cues will facilitate a fascinating area of research into the physiology and therapeutic potential of these cells,” said lead author Somdutta Roy, PhD, Department of Pathology and the UCSF Helen Diller Family Comprehensive Cancer Center.

To read entire article – http://www.ucsf.edu

STEM CELLS REDUCE BRAIN DAMAGE AFTER STROKE

In SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on March 7, 2013 at 9:00 am

stroke

Stroke – Stem Cells Can Reduce Brain Damage

Rescuing a patient from a stroke and restoring cognitive functions are two significant medical challenges today. Blockage of a brain artery, usually by a clot or atherosclerotic plaque, results in reduction in oxygen supply to brain cells. If the supply of oxygen is interrupted for a long time, brain cells die resulting in severe loss of motor and cognitive functions. Therapeutic approaches to prevent the formation of plaques or blood clots are not a hundred percent successful in preventing a stroke. Recent research has focused on aiding regeneration of brain cells after an ischemic stroke and stem cells have been used with reasonable success.

Experiments conducted on rats show that intravenous injection of stem cells derived from adipose tissues as well as mesenchymal stem cells derived from bone marrow supported the recovery of brain cells after a stroke. In these experiments, rats were subjected to a stroke by blocking their middle cerebral artery permanently. Stem cells from bone marrow as well as fat cells were injected 30 minutes after induction and the health of the animals was assessed at 24 hours and 14 days after stroke. In the recovery period, animals injected with stem cells showed increased levels of vascular endothelial growth factor and synaptophysin. The injected stem cells did not migrate to the site of the lesion but presumably acted as a source of neurotrophic growth factors.

In another study, stem cells from the dental pulp of human deciduous teeth (milk teeth) were grafted in the brains of mice one day after induction of a stroke. In some animals, the culture medium in which these cells were grown was used instead of the cells. Mice treated with human dental pulp stem cells and conditioned medium from these cells showed better recovery and neurological outcome than untreated mice. Grafted stem cells as well as the conditioned medium inhibited death of neurons in the recovery period and prevented cell destruction resulting from inflammation. In these experiments, the actual integration of human dental pulp stem cells into the brain tissue occurred at very low frequency.

Both studies present important insights in the process of regeneration of brain cells followed hypoxic and ischemic stroke. Stem cells secrete a number of growth factors which help to promote generation of new neurons post a stroke. The results presented by Yamagata and colleagues where just the culture medium from dental pulp stem cells was effective in restoring brain tissue and neurological functions indicate that a suitable “growth factor cocktail” can be derived from cultures of stem cells to treat stroke. Since intravenous injection of stem cells also helps recovery from stroke, it is easy to deliver such a therapeutic intervention. A xenograft of human dental pulp stem cells was successful in helping mice recover from a stroke. It would be interesting to know whether stem cells from other animal systems have a similar beneficial effect on human neurons as well.

References

Gutierrez-Fernandez M, Rodriguez-Frutos B, Ramos-Cejudo J, Vallejo-Cremades MT, Fuentes B, Cerdan S, & Diez-Tejedor E (2013). Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke. Stem cell research & therapy, 4 (1) PMID: 23356495

Yamagata M, Yamamoto A, Kako E, Kaneko N, Matsubara K, Sakai K, Sawamoto K, & Ueda M (2013). Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice. Stroke; a journal of cerebral circulation, 44 (2), 551-4 PMID: 23238858

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