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Unique route to stem cells: Designer proteins developed to deliver stem cells

Posted: July 13, 2013 at 12:44 am

Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript. In order to enable it, please see these instructions. 15 hours ago The schematic diagram of designer proteins and their binding sites at the Oct4 distal enhancer.

(Phys.org) Researchers have developed a new method to produce stem cells using designed proteins. The new system is more precise and more natural than current techniques and the team believe it could be a more efficient and safer route to producing stem cells.

Stem cells have the potential to be used to replace dying or damaged cells with healthy cells. This repair could have wide-ranging uses in medicine such as organ replacement, bone replacement and treatment of neurodegenerative diseases. This study brings closer to realising the full potential of stem cell technology.

"We have gone down a completely different road to standard practices to produce stem cells from adult cells," says Dr Pentao Liu, senior author from the Wellcome Trust Sanger Institute. "Current techniques to reprogramme cells are inefficient and it's imperative to find other ways to create stem cells."

"We hope that our novel approach to reprogramming cells into stem cells will become a new and safer alternative to current practices."

The team looked at proteins called transcription factors, which regulate the activity of all human genes. Each transcription factor acts to modify the activity of several or many genes.

A key set of these transcription factors are able to convert or reprogramme adult cells into induced pluripotent stem cells or iPS cells. However, these factors also act on many genes other than those involved in reprogramming.

The team developed artificial designer transcription factors to target those key reprogramming genes more accurately, minimizing activity on other genes.

"This is a promising and exciting development in our attempt to produce iPS cells that lend themselves in practical applications," says Dr Xuefei Gao, first author from the Wellcome Trust Sanger Institute. "We have shown that targeting gene-control regions, called enhancers, in this structured way is a very effective in controlling a gene and reprogramming cells to become iPS cells."

In conventional methods, the transcription factors used to programme cells take part in complicated ways - and target many different parts of the genome - as they are used to reprogramme the cells to become stems cells. As a result, the throughput of successfully reprogrammed cells can be low and the additional number of steps can have associated risks, such as affecting genes that can influence tumour development.

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Unique route to stem cells: Designer proteins developed to deliver stem cells

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Global Stem Cells Market – Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 – 2018

Posted: July 13, 2013 at 12:44 am

Albany, New York (PRWEB) July 12, 2013

According to a new market report published by Transparency Market Research "Stem Cells Market (Adult, Human Embryonic , Induced Pluripotent, Rat-Neural, Umbilical Cord, Cell Production, Cell Acquisition, Expansion, Sub-Culture)- Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 - 2018," the market for stem cells was valued at USD 26.23 billion in 2011 and is expected to reach an estimated value of USD 119.51 billion in 2018, growing at a CAGR of 24.2% from 2012 to 2018.

Related Report : Coronary Stents Market http://www.transparencymarketresearch.com/coronary-stents-market.html

Stem cells are undifferentiated cells which are capable of differentiating into any type of cell that make-up the human body and thus, are capable of producing non-regenerative cells such as neural and myocardial cells. This report estimates the market for global stem cells in terms of revenue (USD billion) for the period 2012 2018, keeping 2011 as the base year.

The global stem cells market is mainly segmented into four major sub-types namely market by products, market by technology, market by applications and market by geography. The market by products is segmented into three sub-types, namely adult stem cells, human embryonic stem cells and other type of stem cells. Adult stem cells are further segmented into hematopoietic stem cells, mesenchymal stem cells, neuronal stem cells, dental stem cells and umbilical cord stem cells.

Browse Bolg : Medical Devices Market Research Reports http://medical-devices-market-reports.blogspot.com/

The other types of stem cells include induced pluripotent stem cells, natural rosette cells and very small embryonic like stem cells. The global stem cells market by technology is segmented into four sub-types, namely cell acquisition, cell production, cryopreservation and expansion and sub-culture. Cell acquisition is further segmented into three sub-types, namely bone marrow harvest, apheresis and umbilical cord blood. Cell production is further segmented into therapeutic cloning, in vitro fertilization, isolation and cell culture.

Browse the full report with TOC at http://www.transparencymarketresearch.com/stem-cells-market.html.

The global stem cells market by application is segmented into regenerative medicines and drug discovery and development. Regenerative medicines are further segmented into ten sub-types, namely neurological disorders, orthopedics, cancer, hematological disorders, cardiovascular diseases, injuries, diabetes, liver disorders, incontinence and other disorders like Crohns disease, infertility, immunodeficiency disorders and organ transplants. The global stem cells market is also segmented on the basis of geography into North America, Europe, Asia and rest of the world (RoW) regions and the market in terms of USD billion is provided in this report. The report highlights the market shares of key players in 2011.

The company profiles for some of the key players, namely Advanced Cell Technology Inc., STEMCELL Technologies Inc., Cellular Engineering Technologies Inc., BioTime Inc., Aastrom Biosciences Inc. and California Stem Cell Inc. in terms of company overview, financial overview, business strategies, recent developments and product portfolio is also covered.

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Global Stem Cells Market - Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 - 2018

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Sanger maps unique route to stem cells

Posted: July 13, 2013 at 12:44 am

Cambridge researchers have developed a new method to produce stem cells using designed proteins.

Stem cells have the potential to be used to replace dying or damaged cells with healthy cells. This repair could have wide-ranging uses in medicine such as organ replacement, bone replacement and treatment of neurodegenerative diseases. This study brings closer to realising the full potential of stem cell technology.

We have gone down a completely different road to standard practices to produce stem cells from adult cells, says Dr Pentao Liu, senior author from the Wellcome Trust Sanger Institute.

Current techniques to reprogramme cells are inefficient and its imperative to find other ways to create stem cells. We hope that our novel approach to reprogramming cells into stem cells will become a new and safer alternative to current practices.

The team looked at proteins called transcription factors, which regulate the activity of all human genes. Each transcription factor acts to modify the activity of several or many genes.

A key set of these transcription factors are able to convert or reprogramme adult cells into induced pluripotent stem cells or iPS cells. However, these factors also act on many genes other than those involved in reprogramming.

The team developed artificial designer transcription factors to target those key reprogramming genes more accurately, minimising activity on other genes.

"This is a promising and exciting development in our attempt to produce iPS cells that lend themselves in practical applications, says Dr Xuefei Gao, first author from the Wellcome Trust Sanger Institute. We have shown that targeting gene-control regions, called enhancers, in this structured way is a very effective in controlling a gene and reprogramming cells to become iPS cells.

In conventional methods, the transcription factors used to programme cells take part in complicated ways and target many different parts of the genome as they are used to reprogramme the cells to become stems cells. As a result, the throughput of successfully reprogrammed cells can be low and the additional number of steps can have associated risks, such as affecting genes that can influence tumour development.

The designer transcription factors are extremely accurate. Because this method targets key genes directly and avoids additional genetic detours, it reduces the potential risks linked with standard practices.

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Sanger maps unique route to stem cells

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Researchers Create Inner Ear Using Stem Cells

Posted: July 13, 2013 at 12:44 am

Featured Article Main Category: Ear, Nose and Throat Also Included In: Stem Cell Research Article Date: 12 Jul 2013 - 2:00 PDT

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Scientists have developed a way of using stem cells to create key structures of the inner ear in mice, publishing their findings in the journal Nature.

The Indiana University researchers found that by using a 3D cell-culture method, they were able to persuade stem cells to develop into inner ear sensory epithelium, which detects head movement, gravity and sound. The epithelium contains hair cells, supporting cells and neurons.

A 3D cell-culture method can more closely copy natural tissues and organs than cells grown two-dimensionally. In 3D cell culture, cells can attach to each other and form natural cell-to-cell attachments.

Karl R. Koeheler, one of the researchers in the study, explains:

"The three-dimensional culture allows the cells to self-organize into complex tissues using mechanical cues that are found during embryonic development."

"We were surprised to see that once stem cells are guided to become inner ear precursors and placed in 3D culture, these cells behave as if they knew not only how to become different cell types in the inner ear, but also how to self-organize into a pattern remarkably similar to the native inner ear."

He adds that their initial goal was to make inner ear precursors, cells from which other cells are formed, in the 3D culture method - but when they did testing, thousands of hair cells were found in the culture dish.

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Researchers Create Inner Ear Using Stem Cells

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Injecting iron supplement lets Stanford scientists track transplanted stem cells

Posted: July 13, 2013 at 12:44 am

Public release date: 12-Jul-2013 [ | E-mail | Share ]

Contact: Bruce Goldman 650-725-2106 Stanford University Medical Center

STANFORD, Calif. A new, noninvasive technique for tracking stem cells after transplantation developed by a cross-disciplinary team of radiologists, chemists, statisticians and materials scientists at the Stanford University School of Medicine could help surgeons determine whether a procedure to repair injured or worn-out knees is successful.

The technique, described in a study to be published online July 12 in Radiology, relies on an imaging agent already approved by the U.S. Food and Drug Administration for an entirely different purpose: anemia treatment. Although this study used rodents, the approach is likely to be adapted for use in humans this fall as part of a clinical trial in which mesenchymal stem cells will be delivered to the site of patients' knee injuries. Mesenchymal stem cells are capable of differentiating into bone and cartilage, as well as muscle, fat and tendon, but not into the other cell types that populate the body.

Every year, arthritis accounts for 44 million outpatient visits and 700,000 knee-replacement procedures. But the early repair of cartilage defects in young patients may prevent further deterioration of the joint and the need for knee replacement later in life, said the study's senior author, Heike Daldrup-Link, MD, PhD, an associate professor of radiology and clinician who splits her time between research and treating pediatric patients.

Mesenchymal stem cells have been used with some success in cartilage-repair procedures. "These cells can be easily derived from bone marrow of patients who are going to undergo the knee-repair procedure," said Daldrup-Link, a member of the Molecular Imaging Program at Stanford. "And they can differentiate into the real-life tissues that compose our joints. But here, too, things can go wrong. The newly transferred cells might fail to engraft, or die. They might migrate away. They could develop into tissues other than cartilage, most commonly fibrous scar tissue."

Relatively few transplanted cells go the distance. The ability to monitor the cells' engraftment after they are deposited at a patient's knee-injury site is therefore essential. With the new technique, magnetic resonance imaging can visualize stem cells for several weeks after they have been implanted, giving orthopaedic surgeons a better sense of whether the transplantation was successful.

Until now, the only ways of labeling mesenchymal stem cells so that they could be noninvasively imaged have required their manipulation in the laboratory. Upon extraction, the delicate cells have to be given to lab personnel, incubated with contrast agents, spun in a centrifuge and washed and returned to the surgeons, who then transplant the cells into a patient.

The new technique involves labeling the cells before extraction, while they reside in the donor's bone marrow. For the study, lead authors Aman Khurana, MD, a postdoctoral scholar, and Fanny Chapelin, a research associate, injected ferumoxytol, an FDA-licensed anemia treatment composed of iron-oxide nanoparticles, into rats prior to extracting bone marrow from them. Then, after enriching the mixture for mesenchymal stem cells, the investigators injected it into the sites of knee injuries in recipient rats. They followed the implanted cells' progress for up to four weeks, comparing the results with those obtained both from cells labeled in laboratory dishes and from unlabeled cells.

Daldrup-Link and others previously have used ferumoxytol for stem-cell labeling in a dish. However, mesenchymal stem cells in a laboratory dish take up very little of this substance. Interestingly, the researchers showed in a series of experiments that, ensconced in donor rats' bone marrow, the same cells are avid ferumoxytol absorbers. Even several weeks after transplantation into the recipient rats' knees, the mesenchymal stem cells retain enough iron to provide a strong MRI signal.

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Injecting iron supplement lets Stanford scientists track transplanted stem cells

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Two successful gene therapy trials block inherited diseases in humans

Posted: July 13, 2013 at 12:42 am

Gene therapy: not just for mice.

Genetic traits, like a bulbous nose or balding, give some people reasons to moan about what they inherited from their parents. But more serious genetic flaws can cause debilitating disease. Now, Italian researchers have come up with a way of treating one such inherited disease and reversing another using a promising new method of gene therapy.

The idea behind gene therapy is to replace a faulty gene with a shiny new version that works properly. Modified versions of viruses, which have been sculpted by millions of years of evolution, perfectly penetrate human cells. They act as courriers delivering DNA payloads to defective cells and ensure they are stably inherited.

This deceptively simple idea, though, has been challenging to achieve in practice. The first commercial gene therapy product, Glybera, only received regulatory approval in 2012.

Part of the reason for this is the difficulty of successfully clearing three hurdles at once: delivering replacement genetic information to the exact cells that need help, getting this information safely translated in high enough volumes to overcome the defects, and stopping the immune system from reacting to normal genes when it has grown used to only seeing mangled ones.

Now, a team led by Alessandra Biffi at the San Raffaele Scientific Institute in Milan, Italy, reports inScience that they have developed a new approach that navigates each of these hurdles to treat three children with metachromatic leukodystrophy (MLD), a devastating inherited disease that affects around 1 in 40,000 people.

MLD usually manifests in early childhood and kills patients just a few years after the first symptoms appear. It is caused by a defect in a single gene, ARSA. This gene encodes information used by the lysosome, a piece of recycling machinery used by human cells to break down unwanted material. When this recycling process does not work properly in nerve cells, as is the case with MLD patients, they become filled with rubbish and begin to slowly decline, leading to brain and spinal cord degeneration, as well as sensory deprivation.

Supplying a replacement ARSA gene to affected cells in the nervous system is a tricky task, because these areas are heavily protected. To overcome these defenses, the team employed haematopoietic stem cells (HSCs), which can usually be found nestling quietly in the bone marrow, as stealthy genetic courriers. A tiny number of these cells were harvested from each patient, loaded with benign viruses carrying a working copy of ARSA, and put back into the bloodstream.

These engineered cells either lodged in the bone marrow or continued to travel around the body in the blood, where they corrected defective cells in the nervous system by supplying the normal version of ARSA. Because these were stem cells, they also reproduced to form new blood cells that themselves took on the same supportive roles.

Most MLD patients produce a garbled version of ARSA that has a very low level of activity, nowhere near enough to let the lysosome carry out its normal job. Restoring partial activity is not enough to make a clinical impactlevels must be hiked to make an obvious difference.

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Two successful gene therapy trials block inherited diseases in humans

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New gene therapy hope for rare childhood disease

Posted: July 13, 2013 at 12:42 am

A new type of gene therapy has shown promise in wiping out two rare childhood diseases, apparently without the risks of causing cancer, international researchers said Thursday.

The method used an HIV virus vector and the patients' own blood stem cells to deliver a corrected version of a faulty gene, said the report in the US journal Science.

As a result, six children are doing well, 18 to 32 months after their operations, said lead scientist Luigi Naldini of the San Raffaele Telethon Institute for Gene Therapy in Milan.

"Three years after the start of the clinical trial, the results obtained from the first six patients are very encouraging. The therapy is not only safe, but also effective and able to change the clinical history of these severe diseases."

Three of the children suffer from metachromatic leukodystrophy, a disease of the nervous system which is caused by mutations in the ARSA gene.

Babies with the disease appear healthy when they are born, but as they grow, they start to lose cognitive and motor skills. There is no cure.

The new gene therapy approach has halted progression of the disease in these three children, researchers said.

The other three children in the study have Wiskott-Aldrich syndrome, which is caused by mutations in the WAS gene and results in recurring infections, autoimmune diseases, frequent bleeding, and a high risk of cancer.

The treatment has caused the children's symptoms to lessen or vanish altogether, the researchers said.

Previous attempts at gene therapy for a range of diseases, including Wiskott-Aldrich Syndrome, have shown some success, but over the long term it was discovered that immune-compromised patients sometimes developed blood cancer.

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New gene therapy hope for rare childhood disease

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Gene therapy using lentivirus to treat Wiskott-Aldrich Syndrome promising

Posted: July 13, 2013 at 12:42 am

July 11, 2013 Two Houston researchers from Baylor College of Medicine and Texas Children's Hospital were part of an international team that developed a new gene therapy approach to treatment of Wiskott-Aldrich Syndrome, a fatal inherited form of immunodeficiency.

The new research, led by researchers at the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy was published in Science Express.

The disorder that weakens the body's immune system is caused by a mutation in a gene that encodes the protein WASP. The most often used therapy is a bone marrow or stem cell transplant from a matching donor -- often a sibling or relative. It can be curative for some patients -- mostly those who have a strongly matching donor.

An alternative is to obtain blood stem cells from patient, and, in the laboratory, use gene therapy involving a form of retrovirus to take the normal gene into the cells to correct the defect. The patients are then given back the genetically changed blood cells back.

This approach has been successful in a number of diseases, including who had Wiskott-Aldrich Syndrome. However, over the long term, some patients with immune deficiencies, including those with Wiskott-Aldrich Syndrome, developed blood cancers.

Researchers believe the viral vector used to take the gene into the cell inserted itself next to a oncogene in the DNA, turning it on and causing the cancers.

In this new research, the team used a partially inactivated lentivirus to take the normal gene into the cell, while reducing the risk of the gene inserting next to a cancer-promoting gene.

In these cases for whom there was no matching donor, the researchers led by Alessandro Aiuti of San Raffaele Telethon Institute for Gene Therapy in Milan, Italy; and including Dr. Jordan Orange, professor of pediatrics--rheumatology and Pinaki Banerjee, assistant professor of pediatrics -- human immunology at BCM and Texas Children's, took the patients' own blood stem cells and, in the laboratory, used the lentiviral vector combined with the normal WASP gene to correct the genetic defect in the blood. After a special treatment to eliminate their defective immune system, they received their own blood cells that had been altered to contain the normal WASP gene.

After 20 to 30 months, the three children showed significant improvement. New blood cells had the corrected WASP gene.

Orange referred one of the patients for treatment and saw one of them at a recent meeting. He and Banerjee contributed to the analysis of the gene corrected patient cells at the laboratory level using highly quantitative high-resolution imaging Orange maintains a high-and super resolution imaging facility in the Center for Human Immunobiology at Texas Children's Hospital.

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Gene therapy using lentivirus to treat Wiskott-Aldrich Syndrome promising

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New gene therapy hope for rare childhood diseases

Posted: July 13, 2013 at 12:42 am

WASHINGTON: A new type of gene therapy has shown promise in wiping out two rare childhood diseases, apparently without the risks of causing cancer, international researchers said Thursday.

The method used an HIV virus vector and the patients' own blood stem cells to deliver a corrected version of a faulty gene, said the report in the US journal Science.

As a result, six children are doing well, 18 to 32 months after their operations, said lead scientist Luigi Naldini of the San Raffaele Telethon Institute for Gene Therapy in Milan.

"Three years after the start of the clinical trial, the results obtained from the first six patients are very encouraging. The therapy is not only safe, but also effective and able to change the clinical history of these severe diseases."

Three of the children suffer from metachromatic leukodystrophy, a disease of the nervous system which is caused by mutations in the ARSA gene.

Babies with the disease appear healthy when they are born, but as they grow, they start to lose cognitive and motor skills. There is no cure.

The new gene therapy approach has halted progression of the disease in these three children, researchers said.

The other three children in the study have Wiskott-Aldrich syndrome, which is caused by mutations in the WAS gene and results in recurring infections, autoimmune diseases, frequent bleeding, and a high risk of cancer.

The treatment has caused the children's symptoms to lessen or vanish altogether, the researchers said.

Previous attempts at gene therapy for a range of diseases, including Wiskott-Aldrich Syndrome, have shown some success, but over the long term it was discovered that immune-compromised patients sometimes developed blood cancer.

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New gene therapy hope for rare childhood diseases

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Gene therapy treats children with rare diseases

Posted: July 13, 2013 at 12:42 am

Six kids are healthy, up to three years after treatment

By Tina Hesman Saey

Web edition: July 11, 2013

A virus derived from HIV can safely fix broken immune systems and correct genetic diseases, suggest two new studies involving children with rare conditions.

For both studies, researchers put healthy genes into the childrens own DNA using lentiviruses, in this case genetically engineered versions of HIV that can no longer cause disease. Earlier gene therapy trials using different viruses had a flaw: When the viruses plunked themselves into the patients DNA, they sometimes amped up activity of neighboring cancer-causing genes, leading to leukemia. That side effect, along with the death of a young man participating in another clinical trial, nearly halted gene therapy in the United States in the early 2000s.

Now, researchers led by Luigi Naldini of the San Raffaele Telethon Institute for Gene Therapy in Milan have altered the lentiviruses so that they wont accidently turn on nearby genes. The researchers then infect bone marrow stem cells with lentiviruses carrying the appropriate gene and transplant the stem cells into patients.

In one study, three boys with Wiskott-Aldrich syndrome, an inherited disease that disables the immune system, received gene therapy. Now, two to three years after the therapy, the former bubble boys have healthy immune systems, Naldini and colleagues report July 11 in Science. The boys also show no signs of developing leukemia which should help allay concerns about the teams gene therapy approach, says Todd Rosengart, a surgeon and gene therapy researcher at Baylor College of Medicine in Houston.

In the second trial, Naldini and his colleagues treated three children with a metabolic disease called metachromatic leukodystrophy. Children with the disease lack an important enzyme. As a result, they gradually become paralyzed and suffer damage to their ability to think, dying within a couple of years. Up to two years after the therapy, the children in the study are still making enough of the enzyme to keep their brain and spinal cord working normally with no sign of leukemia, the researchers report in the same issue of Science.

The results are encouraging, says Uta Griesenbach, a gene therapist at Imperial College London. Even after fairly long-term follow up, it appears to be safe and effective. The boys arent out of the woods yet some of the patients in the original gene therapy trials didnt develop cancer until four years after treatment. But Griesenbach says that the children in the new studies dont have warning signs of cancer.

Because the lentiviruses appear safe and work so well, scientists may start doing gene therapy for more common conditions such as Parkinsons disease, says Senlin Li, a medical researcher at the University of Texas Health Science Center at San Antonio.

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Gene therapy treats children with rare diseases

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