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Featured Article Academic Journal Main Category: Bones / Orthopedics Also Included In: Stem Cell Research Article Date: 14 Jun 2012 - 4:00 PDT

Current ratings for: 'Fat Stem Cells Grow Bone Faster And Better'

They write about their work in the 11 June online first issue of a paper published in the new peer-reviewed journal Stem Cells Translational Medicine, which aims to span stem cell research and clinical trials.

The two co-senior authors of the study are Chia Soo, vice chair for research at University of California - Lost Angeles (UCLA) Plastic and Reconstructive Surgery, and Bruno Pault, professor of Orthopedic Surgery at UCLA. Both are members of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Soo told the press that fat tissue is considered a good source of mesenchymal stem cells, the sort that can be coaxed to form various tissue types such as bone, cartilage and muscle, because there is plenty of it and it is easy to get hold of with procedures like liposuction.

One conventional method of growing these stem cells from fat tissue relies on culturing the fat cells for weeks to isolate the stem cells that form bone. These processes can increase the risk of infection and lead to genetic instability.

Another traditional method, called stromal vascular fraction (SVF), uses fresh, non-cultured cells, but it is not easy to extract SVF cells from fat tissue because there are many kinds of them, not all capabale of forming bone.

For this study, the researchers isolated and purified human perivascular stem cells (hPSC) from fat tissue, and using lab animals, showed these cells are a better option for making bone than SVF cells.

They also showed that a growth factor called NELL-1, speeded up bone formation.

Soo told the press:

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Fat Stem Cells Grow Bone Faster And Better

Doctors in Sweden have replaced a vital blocked blood vessel in a 10-year-old girl using the first vein grown in a lab from a patient's own stem cells.

The successful transplant operation, reported online in The Lancet medical journal on Thursday, marks a further advance in the search for ways to make new body parts.

It could open the door to stem cell-based grafts for heart bypass and dialysis patients who lack suitable blood vessels for replacement surgery, and the Swedish team said it is now working with an undisclosed company to commercialize the process.

"I'm very optimistic that in the near future we will be able to get both arteries and veins transplanted on a large scale," said Suchitra Sumitran-Holgersson, professor of transplantation biology at the University of Gothenburg, and a member of the team that performed the operation in March 2011.

The advantage of using tissue grown from a patient's own cells is that there is no risk of organ rejection and hence no need for lifelong immunosuppressive drugs.

Four years ago, a 30-year-old woman received the world's first transplant of a tailor-made windpipe, grown in a similar way by seeding a stripped-down donor organ with her own stem cells. Other such trachea operations have followed since.

The latest case involved a young girl with an obstructed hepatic portal vein, which drains blood from the intestines and spleen to the liver. Its blockage can be fatal.

The team from the University of Gothenburg took a 9 cm (3.5 inch) section of groin vein from a deceased donor and removed all the living cells, leaving just a protein scaffold tube. Stem cells extracted from the girl's bone marrow were then injected onto the tube and two weeks later the graft was implanted.

The new blood vessel immediately restored normal blood flow, the doctors said, although after a year it narrowed and a second stem cell-based graft was needed.

Martin Birchall and George Hamilton of University College London said in a commentary in The Lancet that the Swedish doctors had spared the young girl the trauma of having veins harvested from deep in her neck or leg and avoided the need for a liver transplant.

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Vein grown from stem cells saves 10-year-old girl

14 June 2012 Last updated at 07:25 ET By Eleanor Bradford BBC Scotland Health Correspondent

The first patients to take part in a clinical trial of a stem cell treatment for stroke have seen reductions in their disability, according to doctors.

Six patients in the west of Scotland had human stem cells inserted close to the damaged part of their brain.

After receiving the treatment, they saw improvements in the limb weakness they suffered as a result of their stroke.

Howeve, doctors have cautioned against reading too much into the early results of the clinical trial.

It is the world's first trial of a neural stem cell therapy for stroke.

Stroke is the third largest cause of death and the single largest cause of adult disability in the developed world.

The trial is being conducted at the Institute of Neurological Sciences at the Southern General Hospital in Glasgow, and is being led by Glasgow University neurologist Professor Keith Muir.

He said: "So far we've seen no evidence of any harmful effects. We're dealing with a group of people a long time after a stroke with significant disability and we don't really expect these patients to show any change over time.

"So it's interesting to see that in all the patients so far they have improved slightly over the course of their involvement in the study."

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Stem cells 'help' stroke patients

Scientists from the University of California have discovered a way to eliminate painful bone grafts by using purified fat stem cells to grow a bone. They claim that adipose, or fat, tissue is thought to be an ideal source of mesenchymal stem cells that can be developed into bone, cartilage, muscle and other tissues. These cells are plentiful and an easily be obtained through procedures like liposuction.

Traditionally, cells taken from fat had to be cultured for weeks to isolate the stem cells which could become bone. This method had lot of risk of developing infection and genetic instability. Another way to grow a bone was through stromal vascular fraction (SVF) method.

Now scientists have used a cell-sorting machine to isolate and purify human perivascular stem cells (hPSC) from adipose tissue and showed that the cells worked far better than traditional methods in creating bone.

"The purified human hPSCs formed significantly more bone in comparison to the SVF by all parameters," said Dr Chia Soo, researcher at the University of California. "And these cells are plentiful enough that patients with not much excess body fat can donate their own fat tissue."

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Scientists' claim that fat stem cells are ideal for developing bone much faster and the bone cultivated from the stem cells are likely to have much better quality than bone grown using traditional methods.

"People have shown that culture-derived cells could grow bone, but ours are a fresh cell population, and we didn't have to go through the culture process, which can take weeks," Soo said. "The best bone graft is still your own bone, but that is in limited supply and sometimes not of good quality. What we show here is a faster and better way to create bone that could have clinical applications."

Scientists believe that in future this method will be used to harness a healthy bone. Doctors would take stem cells from the patient's fat tissue, purify that into hPSCs, and replace the patient's own stem cells with hPSCs and NELL-1 in the area where bone is required.

The hPSCs with NELL-1 could grow into bone inside the patient, eliminating the need for painful bone-graft harvestings. The goal is for the process to isolate the hPSCs and add the NELL-1 with a matrix or scaffold to aid cell adhesion in less than an hour, according to the scientists.

"Excitingly, recent studies have already demonstrated the utility of perivascular stem cells for regeneration of disparate tissue types, including skeletal muscle, lung and even myocardium," said Bruno Pault, a professor of orthopedic surgery at the University of California, Los Angeles.

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Purified Fat Stem Cells Can Grow Bone Faster, Say Scientists

LONDON For the first time doctors have successfully transplanted a vein grown with a patient's own stem cells, another example of scientists producing human body parts in the lab.

In this case, the patient was a 10-year-old girl in Sweden who was suffering from a severe vein blockage to her liver. Last March, the girl's doctors decided to make her a new blood vessel to bypass the blocked vein instead of using one of her own or considering a liver transplant.

They took a 9-centimeter (3 -inch) section of vein from a deceased donor, which was stripped of all its cells, leaving just a hollow tube. Using stem cells from the girl's bone marrow, scientists grew millions of cells to cover the vein, a process that took about two weeks. The new blood vessel was then transplanted into the patient.

Because the procedure used her own cells, the girl did not have to take any drugs to stop her immune system from attacking the new vein, as is usually the case in transplants involving donor tissue.

"This is the future for tissue engineering, where we can make tailor-made organs for patients," said Suchitra Sumitran-Holgersson of the University of Gothenburg, one of the study's authors.

She and colleagues published the results of their work online Thursday in the British medical journal Lancet. The work was paid for by the Swedish government.

The science is still preliminary and one year after the vein was transplanted, it needed to be replaced with another lab-grown vein when doctors noticed the blood flow had dropped. Experts from University College London raised questions in an accompanying commentary about how cost-effective the procedure might be, citing "acute pressures" on health systems that might make these treatments impractical for many patients.

Sumitran-Holgersson estimated the cost at between $6,000 and $10,000.

Similar methods have already been used to make new windpipes and urethras for patients. Doctors in Poland have also made blood vessels grown from donated skin cells for dialysis patients.

Patients with the girl's condition are usually treated with a vein transplant from their own leg, a donated vein, or a liver transplant. Those options can be complicated in children and using a donated vein or liver also requires taking anti-rejection medicines.

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Doctors make new vein using patient's own stem cells for transplant into 10-year-old girl

LONDONFor the first time doctors have successfully transplanted a vein grown with a patient's own stem cells, another example of scientists producing human body parts in the lab.

In this case, the patient was a 10-year-old girl in Sweden who was suffering from a severe vein blockage to her liver. Last March, the girl's doctors decided to make her a new blood vessel to bypass the blocked vein instead of using one of her own or considering a liver transplant.

They took a 9-centimeter (3 1/2-inch) section of vein from a deceased donor, which was stripped of all its cells, leaving just a hollow tube. Using stem cells from the girl's bone marrow, scientists grew millions of cells to cover the vein, a process that took about two weeks. The new blood vessel was then transplanted into the patient.

Because the procedure used her own cells, the girl did not have to take any drugs to stop her immune system from attacking the new vein, as is usually the case in transplants involving donor tissue.

"This is the future for tissue engineering, where we can make tailor-made organs for patients," said Suchitra Sumitran-Holgersson of the University of Gothenburg, one of the study's authors.

She and colleagues published the results of their work online Thursday in the British medical journal Lancet. The work was paid for by the Swedish government.

The science is still preliminary and one year after the vein was transplanted, it needed to be replaced with another lab-grown vein when doctors noticed the blood flow had dropped. Experts from University College London raised questions in an accompanying commentary about how cost-effective the procedure might be, citing "acute pressures" on health systems that might make these treatments impractical for many patients.

Sumitran-Holgersson estimated the cost at between $6,000 and $10,000.

Similar methods have already been used to make new windpipes and urethras for patients. Doctors in Poland have also made blood vessels grown from donated skin cells for dialysis patients.

Patients with the girl's condition are usually treated with a vein transplant from their own leg, a donated vein, or a liver transplant. Those options can be complicated in children and using a donated vein or liver also requires taking anti-rejection medicines.

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Doctors make new vein with girl's own stem cells

By Makiko Kitamura - 2012-06-13T22:30:00Z

The first vein grown from a patients own stem cells was successfully transplanted into a 10-year-old girl, potentially offering a way for those lacking healthy veins to undergo dialysis or heart bypass surgery.

A team led by Michael Olausson of the University of Gothenburg took a 9-centimeter (3.5-inch) segment of vein from a human donor and removed all living cells, the Swedish researchers wrote in a study in The Lancet medical journal today. The resulting protein scaffolding was injected with stem cells from the girls bone marrow, and two weeks later was implanted in the patient, who had a blockage in the vein that carries blood from the spleen and intestines to the liver.

The result points to what may be a safer source of stem cells, the building blocks of life which can grow into any type of tissue in the body. Using cells from the patient may limit the risk that the immune system would attack the transplant, which can occur with tissue taken from healthy people and given to the sick. The girl hasnt developed signs of rejection, even without taking drugs to suppress her immune system, the researchers said.

The successful procedure establishes the feasibility and safety of a novel paradigm for treatment, the researchers wrote in the study. Our work opens interesting new areas of research, including trying to reproduce arteries for surgical use in patients.

The recipient had no complications from the operation, and a year later, has grown 6 centimeters and gained 5 kilograms (11 pounds) in weight.

Olausson and colleagues report suggests that tissue- engineered vascular grafts are promising, but one-off experiences such as the procedure they describe need to be converted into full clinical trials in key target populations, Martin Birchall and George Hamilton, professors at the University College London, wrote in a commentary accompanying the Lancet publication.

The study was funded by the Swedish government.

To contact the reporter on this story: Makiko Kitamura in London at mkitamura1@bloomberg.net

To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

Excerpt from:
First Vein Grown From Human Stem Cells Transplanted

ScienceDaily (June 13, 2012) With their potential to treat a wide range of diseases and uncover fundamental processes that lead to those diseases, embryonic stem (ES) cells hold great promise for biomedical science. A number of hurdles, both scientific and non-scientific, however, have precluded scientists from reaching the holy grail of using these special cells to treat heart disease, diabetes, Alzheimer's and other diseases.

In a paper published June 13 in Nature, scientists at the Salk Institute for Biological Studies report discovering that ES cells cycle in and out of a "magical state" in the early stages of embryo development, during which a battery of genes essential for cell potency (the ability of a generic cell to differentiate, or develop, into a cell with specialized functions) is activated. This unique condition, called totipotency, gives ES cells their unique ability to turn into any cell type in the body, thus making them attractive therapeutic targets.

"These findings," says senior author Samuel L. Pfaff, a professor in Salk's Gene Expression Laboratory, "give new insight into the network of genes important to the developmental potential of cells. We've identified a mechanism that resets embryonic stem cells to a more youthful state, where they are more plastic and therefore potentially more useful in therapeutics against disease, injury and aging."

ES cells are like silly putty that can be induced, under the right circumstances, to become specialized cells-for example, skin cells or pancreatic cells-in the body. In the initial stages of development, when an embryo contains as few as five to eight cells, the stem cells are totipotent and can develop into any cell type. After three to five days, the embryo develops into a ball of cells called a blastocyst. At this stage, the stem cells are pluripotent, meaning they can develop into almost any cell type. In order for cells to differentiate, specific genes within the cells must be turned on.

Pfaff and his colleagues performed RNA sequencing (a new technology derived from genome-sequencing to monitor what genes are active) on immature mouse egg cells, called oocytes, and two-cell-stage embryos to identify genes that are turned on just prior to and immediately following fertilization. Pfaff's team discovered a sequence of genes tied to this privileged state of totipotency and noticed that the genes were activated by retroviruses adjacent to the stem cells.

Nearly 8 percent of the human genome is made up of ancient relics of viral infections that occurred in our ancestors, which have been passed from generation to generation but are unable to produce infections. Pfaff and his collaborators found that cells have used some of these viruses as a tool to regulate the on-off switches for their own genes. "Evolution has said, 'We'll make lemonade out of lemons, and use these viruses to our advantage,'" Pfaff says. Using the remains of ancient viruses to turn on hundreds of genes at a specific moment of time in early embryo development gives cells the ability to turn into any type of tissue in the body.

From their observations, the Salk scientists say these viruses are very tightly controlled-they don't know why-and active only during a short window during embryonic development. The researchers identified ES cells in early embryogenesis and then further developed the embryos and cultured them in a laboratory dish. They found that a rare group of special ES cells activated the viral genes, distinguishing them from other ES cells in the dish. By using the retroviruses to their advantage, Pfaff says, these rare cells reverted to a more plastic, youthful state and thus had greater developmental potential.

Pfaff's team also discovered that nearly all ES cells cycle in and out of this privileged form, a feature of ES cells that has been underappreciated by the scientific community, says first author Todd S. Macfarlan, a former postdoctoral researcher in Pfaff's lab who recently accepted a faculty position at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. "If this cycle is prevented from happening," he says, "the full range of cell potential seems to be limited."

It is too early to tell if this "magical state" is an opportune time to harvest ES cells for therapeutic purposes. But, Pfaff adds, by forcing cells into this privileged status, scientists might be able to identify genes to assist in expanding the types of tissue that can be produced.

"There's tremendous hype over the practical applications of embryonic stem cells in clinical situations," he says. "The struggle in labs throughout the world is that the smallest changes in environmental conditions could subtly and unpredictably have an effect on these cells. So, the more we know about the basic requirements needed for these cells to be able to generate a full range of tissue types, the better off we'll be." While the findings shed light on the basic biology of embryonic stem cells, Pfaff says there is still a "long way to go" in terms of their practical, clinical value.

Continued here:
'Magical state' of embryonic stem cells may help overcome hurdles to therapeutics

June 12, 2012

The use of stem-cells building-block cells that are harvested from embryos or adults to treat heart disease could rely on faith as much as it does science, after billions of dollars in research has not produced the results that researchers have been looking for.

Questions and concerns on the topic arose during the recent opening of the multi-million-dollar Scottish Center for Regenerative Medicine (SCRM) in Edinburgh, chaired by Sir Ian Wilmut, the renowned scientist whose Dolly the sheep clone in 1996, was a groundbreaking step in stem cell technology.

During the opening ceremonies of the Center, Christine Mummery of the Leiden University Medical Center in the Netherlands discussed how a 2001 claim, based on mice experimentation, indicated that bone-marrow cells could mend heart damaged by coronary disease, caused a mad rush of people to the clinics looking for a cure-all.

With nothing in the way of systematic research in animals, the first patients were being treated within a year, prematurely by Mummerys account. She argued that the paper that launched the mass stampede was completely wrong, and subsequent studies proved that. But despite the findings, the 2001 paper has never been withdrawn.

Norwegian professor Harald Arnesen in 2007 voiced his concerns over those heart trials as well. He concluded that they were not convincing and that one German team had achieved striking results only because the control group had done particularly badly. Arnesen called for a moratorium on this kind of stem-cell therapy, based on that research.

But neither Arnesen, nor Mummery, could deter clinicians. Another trial, the largest to date, began in January 2012 and included 3,000 heart-attack patients recruited from across Europe. The trial was funded by the European Union as well.

The idea behind the trials is straightforward. During a heart attack, a clogged blood vessel starves heart muscle of oxygen. Up to a billion heart muscle cells, called cardiomyocytes, can be damaged, and the body responds by replacing them with relatively inflexible scar tissue, which can lead to fatal heart failure.

What is notably surprising, explained Mummery, is that stem cells come in many different forms: Embryonic stem cells are the building-blocks of the body and have the potential to turn into all 200 cell types found in the human body. Adult stem cells, however, are limited in what they can do. For example, bone marrow stem cells only generate blood cells.

So, the 2001 study claiming that bone marrow stem cells could turn into healthy heart muscle was a surprising and exciting claim, although a bold move.

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Some Stem-Cells May Not Be The Answer For Heart Disease

By Daily Mail Reporter

PUBLISHED: 07:22 EST, 11 June 2012 | UPDATED: 07:53 EST, 11 June 2012

Hope: The technique of growing new bones could one day be used to replace serious breaks and treat degenerative illnesses

Scientists have successfully grown living bones in a laboratory using stem cells, in a technique that could in future be used to replace shattered limbs, treat osteoporosis and arthritis and fix defects such as cleft palate.

The researchers took around a month to transform stem cells originally taken from fat tissue into sections of fully-formed bone up to several centimetres long.

Standard bone grafts involve two procedures, to cut bone from elsewhere in the patient's body before transplanting it into the damaged area, which carry the risk of infection and complications. Bone can also be obtained from donations, but this brings the chance of rejection.

The new method would allow bones to be custom made to shape outside the body, using the patients own stem cells, removing the need for a potentially traumatic operation and reducing the likelihood of rejection.

So far the research has been carried out only on animals but a patient trial is planned for later this year.

The Israeli technology, developed by biotech company Bonus BioGroup and researchers at the Technion Institute of Research, involves growing the bone to fit the exact shape and size of the damaged area.

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Scientists grow living bone out of stem cells in bid to treat arthritis, osteoperosis and shattered limbs