The nuclei of brain stem cells in some Parkinson's patients become misshapen with age. The discovery opens up new ways to target the disease.

Nubby nucleus: Brain cells from a deceased Parkinsons patient have deformed nuclei (right) compared with normal brain cells from an individual of a similar age. Merce Marti and Juan Carlos Izpisua Belmonte

Stem cells in the brains of some Parkinson's patients are increasingly damaged as they age, an effect that eventually diminishes their ability to replicate and differentiate into mature cell types. Researchers studied neural stem cells created from patients' own skin cells to identify the defects. The findings offer a new focus for therapeutics that target the cellular change.

The report, published today in Nature, takes advantage of the ability to model diseases in cell culture by turning patient's own cells first into so-called induced pluripotent stem cells and then into disease-relevant cell typesin this case, neural stem cells. The basis of these techniques was recognized with a Nobel Prize in medicine last week.

The authors studied cells taken from patients with a heritable form of Parkinson's that stems from mutations in a gene. After growing several generation of neural stem cells derived from patients with that mutation, they saw the cell nuclei start to develop abnormal shapes. Those abnormalities compromise the survival of the neural stem cells, says study coauthor Ignacio Sancho-Martinez of the Salk Institute for Biological Studies in La Jolla, California.

Today's study "brings to light a new avenue for trying to figure out the mechanism of Parkinson's," says Scott Noggle of the New York Stem Cell Foundation. It also provides a new set of therapeutic targets: "Drugs that target or modify the activity [of the gene] could be applicable to Parkinson's patients. This gives you a handle on what to start designing drug screens around."

The strange nuclei were also seen in patients who did not have a known genetic basis for Parkinson's disease. The authors suggest this indicates that dysfunctional neural stem cells could contribute to Parkinson's. While that conclusion is "highly speculative," says Ole Isacson, a neuroscientist at Harvard Medical School, the study demonstrates the "wealth of data and information that we now can gain from iPS cells."

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Stem Cells Reveal Defect in Parkinson's Cells

Stem cell study may help to unravel how a genetic mutation leads to Parkinson's symptoms

Newswise LA JOLLA, CA----By reprogramming skin cells from Parkinson's disease patients with a known genetic mutation, researchers at the Salk Institute for Biological Studies have identified damage to neural stem cells as a powerful player in the disease. The findings, reported online October 17th in Nature, may lead to new ways to diagnose and treat the disease.

The scientists found that a common mutation to a gene that produce the enzyme LRRK2, which is responsible for both familial and sporadic cases of Parkinson's disease, deforms the membrane surrounding the nucleus of a neural stem cell. Damaging the nuclear architecture leads to destruction of these powerful cells, as well as their decreased ability to spawn functional neurons, such as the ones that respond to dopamine.

The researchers checked their laboratory findings with brain samples from Parkinson's disease patients and found the same nuclear envelope impairment.

"This discovery helps explain how Parkinson's disease, which has been traditionally associated with loss of neurons that produce dopamine and subsequent motor impairment, could lead to locomotor dysfunction and other common non-motor manifestations, such as depression and anxiety," says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory, who led the research team. "Similarly, current clinical trials explore the possibility of neural stem cell transplantation to compensate for dopamine deficits. Our work provides the platform for similar trials by using patient-specific corrected cells. It identifies degeneration of the nucleus as a previously unknown player in Parkinson's."

Although the researchers say that they don't yet know whether these nuclear aberrations cause Parkinson's disease or are a consequence of it, they say the discovery could offer clues about potential new therapeutic approaches.

For example, they were able to use targeted gene-editing technologies to correct the mutation in patient's nuclear stem cells. This genetic correction repaired the disorganization of the nuclear envelope, and improved overall survival and functioning of the neural stem cells.

They were also able to chemically inhibit damage to the nucleus, producing the same results seen with genetic correction. "This opens the door for drug treatment of Parkinson's disease patients who have this genetic mutation," says Belmonte.

The new finding may also help clinicians better diagnose this form of Parkinson's disease, he adds. "Due to the striking appearance in patient samples, nuclear deformation parameters could add to the pool of diagnostic features for Parkinson's disease," he says.

The research team, which included scientists from China, Spain, and the University of California, San Diego, and Scripps Research Institute, made their discoveries using human induced pluripotent stem cells (iPSCs). These cells are similar to natural stem cells, such as embryonic stem cells, except that they are derived from adult cells. While generation of these cells has raised expectations within the biomedical community due to their transplant potential - the idea that they could morph into tissue that needs to be replaced - they also provide exceptional research opportunities, says Belmonte.

Go here to see the original:
Scientists Pinpoint Key Player in Parkinson's Disease Neuron Loss

ScienceDaily (Oct. 19, 2012) By reprogramming skin cells from Parkinson's disease patients with a known genetic mutation, researchers at the Salk Institute for Biological Studies have identified damage to neural stem cells as a powerful player in the disease. The findings, reported online October 17th in Nature, may lead to new ways to diagnose and treat the disease.

The scientists found that a common mutation to a gene that produce the enzyme LRRK2, which is responsible for both familial and sporadic cases of Parkinson's disease, deforms the membrane surrounding the nucleus of a neural stem cell. Damaging the nuclear architecture leads to destruction of these powerful cells, as well as their decreased ability to spawn functional neurons, such as the ones that respond to dopamine.

The researchers checked their laboratory findings with brain samples from Parkinson's disease patients and found the same nuclear envelope impairment.

"This discovery helps explain how Parkinson's disease, which has been traditionally associated with loss of neurons that produce dopamine and subsequent motor impairment, could lead to locomotor dysfunction and other common non-motor manifestations, such as depression and anxiety," says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory, who led the research team. "Similarly, current clinical trials explore the possibility of neural stem cell transplantation to compensate for dopamine deficits. Our work provides the platform for similar trials by using patient-specific corrected cells. It identifies degeneration of the nucleus as a previously unknown player in Parkinson's."

Although the researchers say that they don't yet know whether these nuclear aberrations cause Parkinson's disease or are a consequence of it, they say the discovery could offer clues about potential new therapeutic approaches.

For example, they were able to use targeted gene-editing technologies to correct the mutation in patient's nuclear stem cells. This genetic correction repaired the disorganization of the nuclear envelope, and improved overall survival and functioning of the neural stem cells.

They were also able to chemically inhibit damage to the nucleus, producing the same results seen with genetic correction. "This opens the door for drug treatment of Parkinson's disease patients who have this genetic mutation," says Belmonte.

The new finding may also help clinicians better diagnose this form of Parkinson's disease, he adds. "Due to the striking appearance in patient samples, nuclear deformation parameters could add to the pool of diagnostic features for Parkinson's disease," he says.

The research team, which included scientists from China, Spain, and the University of California, San Diego, and Scripps Research Institute, made their discoveries using human induced pluripotent stem cells (iPSCs). These cells are similar to natural stem cells, such as embryonic stem cells, except that they are derived from adult cells. While generation of these cells has raised expectations within the biomedical community due to their transplant potential -- the idea that they could morph into tissue that needs to be replaced -- they also provide exceptional research opportunities, says Belmonte.

"We can model disease using these cells in ways that are not possible using traditional research methods, such as established cell lines, primary cultures and animal models," he says.

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Key player in Parkinson's disease neuron loss pinpointed

By Charles Choi, LiveScience contributor

Death will come for us all one day, but life will not fade from our bodies all at once. After our lungs stop breathing, our hearts stop beating, our minds stop racing, our bodies cool, and long after our vital signs cease, little pockets of cells can live for days, even weeks. Now scientists have harvested such cells from the scalps and brain linings of human corpses and reprogrammed them into stem cells.

In other words, dead people can yield living cells that can be converted into any cell or tissue in the body.

As such, this work could help lead to novel stem cell therapies and shed light on a variety of mental disorders, such as schizophrenia, autism and bipolar disorder, which may stem from problems with development, researchers say.

Making stem cells Mature cells can be made or induced to become immature cells, known as pluripotent stem cells, which have the ability to become any tissue in the body and potentially can replace cells destroyed by disease or injury. This discovery was honored last week with the Nobel Prize.

Past research showed this same process could be carried out with so-called fibroblasts taken from the skin of human cadavers. Fibroblasts are the most common cells of connective tissue in animals, and they synthesize the extracellular matrix, the complex scaffolding between cells. [ Science of Death: 10 Tales from the Crypt ]

Cadaver-collected fibroblasts can be reprogrammed into induced pluripotent stem cells using chemicals known as growth factors that are linked with stem cell activity. Reprogrammed cells could then develop into a multitude of cell types, including the neurons found in the brain and spinal cord. However, bacteria and fungi on the skin can wreak havoc on the culturing processes used to grow cells in labs, making the process tricky to successfully carry out.

Now scientists have taken fibroblasts from the scalps and the brain linings of 146 human brain donors and grown induced pluripotent stem cells from them as well.

"We were able to culture living cells from deceased individuals on a larger scale than ever done before," researcher Thomas Hyde, a neuroscientist, neurologist and chief operating officer at the Lieber Institute for Brain Development in Baltimore, told LiveScience. Previous studies had only grown fibroblasts from a total of about a half-dozen cadavers.

The bodies had been dead up to nearly two days before scientists collected tissues from them. The corpses had been kept cool in the morgue, but not frozen.

See original here:
New life for the dead: Stem cells from corpse scalp

Death will come for us all one day, but life will not fade from our bodies all at once. After our lungs stop breathing, our hearts stop beating, our minds stop racing, our bodies cool, and long after our vital signs cease, little pockets of cells can live for days, even weeks. Now scientists have harvested such cells from the scalps and brain linings of human corpses and reprogrammed them into stem cells.

In other words, dead people can yield living cells that can be converted into any cell or tissue in the body.

As such, this work could help lead to novel stem cell therapies and shed light on a variety of mental disorders, such as schizophrenia, autism and bipolar disorder, which may stem from problems with development, researchers say.

Making stem cells

Mature cells can be made or induced to become immature cells, known as pluripotent stem cells, which have the ability to become any tissue in the body and potentially can replace cells destroyed by disease or injury. This discovery was honored last week with the Nobel Prize.

Past research showed this same process could be carried out with so-called fibroblasts taken from the skin of human cadavers. Fibroblasts are the most common cells of connective tissue in animals, and they synthesize the extracellular matrix, the complex scaffolding between cells. [Science of Death: 10 Tales from the Crypt]

Cadaver-collected fibroblasts can be reprogrammed into induced pluripotent stem cells using chemicals known as growth factors that are linked with stem cell activity. Reprogrammed cells could then develop into a multitude of cell types, including the neurons found in the brain and spinal cord. However, bacteria and fungi on the skin can wreak havoc on the culturing processes used to grow cells in labs, making the process tricky to successfully carry out.

Now scientists have taken fibroblasts from the scalps and the brain linings of 146 human brain donors and grown induced pluripotent stem cells from them as well.

"We were able to culture living cells from deceased individuals on a larger scale than ever done before," researcher Thomas Hyde, a neuroscientist, neurologist and chief operating officer at the Lieber Institute for Brain Development in Baltimore, told LiveScience. Previous studies had only grown fibroblasts from a total of about a half-dozen cadavers.

The bodies had been dead up to nearly two days before scientists collected tissues from them. The corpses had been kept cool in the morgue, but not frozen.

Continued here:
Human Cadaver Brains May Provide New Stem Cells

ScienceDaily (Oct. 15, 2012) A new method of using adult stem cells as a model for the hereditary condition Gaucher disease could help accelerate the discovery of new, more effective therapies for this and other conditions such as Parkinson's, according to new research from the University of Maryland School of Medicine.

Scientists at the University of Maryland School of Medicine reprogrammed stem cells to develop into cells that are genetically similar to and react to drugs in a similar way as cells from patients with Gaucher disease. The stem cells will allow the scientists to test potential new therapies in a dish, accelerating the process toward drug discovery, according to the paper published online in the journal the Proceedings of the National Academy of Sciences (PNAS) on Oct. 15.

"We have created a model for all three types of Gaucher disease, and used stem cell-based tests to evaluate the effectiveness of therapies," says senior author Ricardo Feldman, Ph.D., associate professor of microbiology and immunology at the University of Maryland School of Medicine, and a research scientist at the University of Maryland Center for Stem Cell Biology and Regenerative Medicine. "We are confident that this will allow us to test more drugs faster, more accurately and more safely, bringing us closer to new treatments for patients suffering from Gaucher disease. Our findings have potential to help patients with other neurodegenerative diseases as well. For example, about 10 percent of Parkinson's disease patients carry mutations in the recessive gene for Gaucher disease, making our research possibly significant for Parkinson's disease as well."

Gaucher disease is the most frequent lipid-storage disease. It affects 1 in 50,000 people in the general population. It is most common in Ashkenazi Jews, affecting 1 in 1,000 among that specific population. The disease occurs in three subtypes -- Type 1 is the mildest and most common form of the disease, causing symptoms such as enlarged livers and spleens, anemia and bone disease. Type 2 causes very serious brain abnormalities and is usually fatal before the age of two, while Type 3 affects children and adolescents.

The condition is a recessive genetic disorder, meaning that both parents must be carriers for a child to suffer from Gaucher. However, said Dr. Feldman, studies have found that people with only one copy of a mutated Gaucher gene -- those known as carriers -- are at an increased risk of developing Parkinson's disease.

"This science is a reflection of the mission of the University of Maryland School of Medicine -- to take new treatments from bench to bedside, from the laboratory to patients, as quickly as possible," says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. "We are excited to see where this research goes next, bringing new hope to Gaucher patients and their families."

Dr. Feldman and his colleagues used the new reprogramming technology developed by Shinja Yamanaka in Japan, who was recognized with this year's Nobel Prize for Medicine or Physiology. Scientists engineered cells taken from the skin of Gaucher patients, creating human induced pluripotent stem cells, known as hiPSC -- stem cells that are theoretically capable of forming any type of cell in the body. Scientists differentiated the cells to form white blood cells known as macrophages and neuronal cells.

A key function of macrophages in the body is to ingest and eliminate damaged or aged red blood cells. In Gaucher disease, the macrophages are unable to do so -- they can't digest a lipid present in the red blood cell membrane. The macrophages become engorged with lipid and cannot completely clear the ingested red blood cells. This results in blockage of membrane transport pathways in the macrophages lodged in the bone marrow, spleen and liver. The macrophages that the scientists created from the reprogrammed stem cells exhibited this characteristic hallmark of the macrophages taken from Gaucher patients.

To further test the stem cells, the scientists administered a recombinant enzyme that is effective in treating Gaucher patients with Type 1 disease. When the cells were treated with the enzyme, the function of the macrophages was restored -- they completely cleared the red blood cells.

"The creation of these stem cell lines is a lovely piece of stem cell research," said Curt Civin, M.D., professor of pediatrics and physiology, associate dean for research and founding director of the Center for Stem Cell Biology & Regenerative Medicine at the University of Maryland School of Medicine. "Dr. Feldman is already using these Gaucher patient-derived macrophages to better understand the disease fundamentals and to find novel medicines for Gaucher disease treatment. A major goal of our Center for Stem Cell Biology & Regenerative Medicine is to translate our fundamental discoveries into innovative and practical clinical applications that will enhance the understanding, diagnosis, treatment, and prevention of many human diseases. Clinical applications include not only transplantation of stem cells, but also the use of stem cells for drug discovery as Dr. Feldman's studies so beautifully illustrate."

See more here:
Stem cell model for hereditary disease developed

Washington, October 13 (ANI): In a new study, researchers have taken the first steps to create neural-like stem cells from muscle tissue in animals.

"Reversing brain degeneration and trauma lesions will depend on cell therapy, but we can't harvest neural stem cells from the brain or spinal cord without harming the donor," Osvaldo Delbono, lead author of the study from Wake Forest Baptist Medical Center, said.

"Skeletal muscle tissue, which makes up 50 percent of the body, is easily accessible and biopsies of muscle are relatively harmless to the donor, so we think it may be an alternative source of neural-like cells that potentially could be used to treat brain or spinal cord injury, neurodegenerative disorders, brain tumours and other diseases, although more studies are needed," Delbono said.

In an earlier study, the Wake Forest Baptist team isolated neural precursor cells derived from skeletal muscle of adult transgenic mice.

In the current research, the team isolated neural precursor cells from in vitro adult skeletal muscle of various species including non-human primates and aging mice, and showed that these cells not only survived in the brain, but also migrated to the area of the brain where neural stem cells originate.

Another issue the researchers investigated was whether these neural-like cells would form tumours, a characteristic of many types of stem cells. To test this, the team injected the cells below the skin and in the brains of mice, and after one month, no tumours were found.

"Right now, patients with glioblastomas or other brain tumours have very poor outcomes and relatively few treatment options," Alexander Birbrair, first author of the study, said.

"Because our cells survived and migrated in the brain, we may be able to use them as drug-delivery vehicles in the future, not only for brain tumours but also for other central nervous system diseases," he added.

The findings of the study have been published online in the journals Experimental Cell Research and Stem Cell Research. ANI)

See the rest here:
Stem cells from muscle tissue 'may help cure neurodegenerative diseases'

By Mary Brophy Marcus HealthDay Reporter

FRIDAY, Oct. 12 (HealthDay News) -- Autism researchers have been given the go-ahead by the U.S. Food and Drug Administration to launch a small study in children with autism that evaluates whether a child's own umbilical cord blood may be an effective treatment.

Thirty children with the disorder, aged 2 to 7, will receive injections of their own stem cells from umbilical cord blood banked by their parents after their births. All of the cord blood comes from the Cord Blood Registry, the world's largest stem cell bank.

Scientists at Sutter Neuroscience Institute, in Sacramento, Calif., said the placebo-controlled study will evaluate whether the stem cell therapy helps improve language and behavior in the youngsters.

There is anecdotal evidence that stem cell infusions may have a benefit in other conditions such as cerebral palsy, said lead study investigator Dr. Michael Chez, director of pediatric neurology at the institute.

"We're hoping we'll see in the autism population a group of patients that also responds," Chez said. Other autism and stem cell research is going on abroad, but this study is the first to use a child's own cord blood stem cells.

Chez said the study will involve only patients whose autism is not linked to a genetic syndrome or brain injury, and all of the children will eventually receive the stem cells.

Two infusions will take place during the 13-month study. At the start of the research, the children will be split into two groups, half receiving an infusion of cord blood stem cells and half receiving a placebo. At six months, the groups will swap therapies. The infusions will be conducted on an outpatient basis with close monitoring, Chez said.

"We're working with Sutter Children's Hospital, who does our oncology infusions with the same-age children," he said. "They are very experienced nurses who work with preschool and school-age kids to help them get through medical experiences."

Each child and his or her parents will be given a private room with a television and videos, beverages, and perhaps a visit from the hospital's canine therapy dog, and then a topical anesthetic will be applied to the arm to numb the skin before intravenous needle placement. A hematology expert will be giving the infusions and monitoring for safety, said Chez, who noted that each child will be watched closely for an hour and a half before heading home. They will be seen the next day as well for a safety check.

Link:
Could Stem Cells Treat Autism? Newly Approved Study May Tell

ScienceDaily (Oct. 12, 2012) Scientists at Wake Forest Baptist Medical Center have taken the first steps to create neural-like stem cells from muscle tissue in animals.

Details of the work are published in two complementary studies published in the September online issues of the journals Experimental Cell Research and Stem Cell Research.

"Reversing brain degeneration and trauma lesions will depend on cell therapy, but we can't harvest neural stem cells from the brain or spinal cord without harming the donor," said Osvaldo Delbono, M.D., Ph.D., professor of internal medicine at Wake Forest Baptist and lead author of the studies.

"Skeletal muscle tissue, which makes up 50 percent of the body, is easily accessible and biopsies of muscle are relatively harmless to the donor, so we think it may be an alternative source of neural-like cells that potentially could be used to treat brain or spinal cord injury, neurodegenerative disorders, brain tumors and other diseases, although more studies are needed."

In an earlier study, the Wake Forest Baptist team isolated neural precursor cells derived from skeletal muscle of adult transgenic mice (PLOS ONE, Feb. 3, 2011).

In the current research, the team isolated neural precursor cells from in vitro adult skeletal muscle of various species including non-human primates and aging mice, and showed that these cells not only survived in the brain, but also migrated to the area of the brain where neural stem cells originate.

Another issue the researchers investigated was whether these neural-like cells would form tumors, a characteristic of many types of stem cells. To test this, the team injected the cells below the skin and in the brains of mice, and after one month, no tumors were found.

"Right now, patients with glioblastomas or other brain tumors have very poor outcomes and relatively few treatment options," said Alexander Birbrair, a doctoral student in Delbono's lab and first author of these studies. "Because our cells survived and migrated in the brain, we may be able to use them as drug-delivery vehicles in the future, not only for brain tumors but also for other central nervous system diseases."

In addition, the Wake Forest Baptist team is now conducting research to determine if these neural-like cells also have the capability to become functioning neurons in the central nervous system.

Co-authors of the studies are Tan Zhang, Ph.D., Zhong-Min Wang, M.S., Maria Laura Messi, M.S., Akiva Mintz, M.D., Ph.D., of Wake Forest Baptist, and Grigori N. Enikolopov, Ph.D., of Cold Spring Harbor Laboratory.

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Neural-like stem cells from muscle tissue may hold key to cell therapies for neurodegenerative diseases

Public release date: 12-Oct-2012 [ | E-mail | Share ]

Contact: Marguerite Beck marbeck@wakehealth.edu 336-716-2415 Wake Forest Baptist Medical Center

WINSTON-SALEM, N.C. Oct. 12, 2012 Scientists at Wake Forest Baptist Medical Center have taken the first steps to create neural-like stem cells from muscle tissue in animals. Details of the work are published in two complementary studies published in the September online issues of the journals Experimental Cell Research and Stem Cell Research.

"Reversing brain degeneration and trauma lesions will depend on cell therapy, but we can't harvest neural stem cells from the brain or spinal cord without harming the donor," said Osvaldo Delbono, M.D., Ph.D., professor of internal medicine at Wake Forest Baptist and lead author of the studies.

"Skeletal muscle tissue, which makes up 50 percent of the body, is easily accessible and biopsies of muscle are relatively harmless to the donor, so we think it may be an alternative source of neural-like cells that potentially could be used to treat brain or spinal cord injury, neurodegenerative disorders, brain tumors and other diseases, although more studies are needed."

In an earlier study, the Wake Forest Baptist team isolated neural precursor cells derived from skeletal muscle of adult transgenic mice (PLOS One, Feb.3, 2011).

In the current research, the team isolated neural precursor cells from in vitro adult skeletal muscle of various species including non-human primates and aging mice, and showed that these cells not only survived in the brain, but also migrated to the area of the brain where neural stem cells originate.

Another issue the researchers investigated was whether these neural-like cells would form tumors, a characteristic of many types of stem cells. To test this, the team injected the cells below the skin and in the brains of mice, and after one month, no tumors were found.

"Right now, patients with glioblastomas or other brain tumors have very poor outcomes and relatively few treatment options," said Alexander Birbrair, a doctoral student in Delbono's lab and first author of these studies. "Because our cells survived and migrated in the brain, we may be able to use them as drug-delivery vehicles in the future, not only for brain tumors but also for other central nervous system diseases."

In addition, the Wake Forest Baptist team is now conducting research to determine if these neural-like cells also have the capability to become functioning neurons in the central nervous system.

Read the original here:
Stem cells from muscle tissue may hold key to cell therapies for neurodegenerative diseases

ScienceDaily (Oct. 11, 2012) The generation of functional thyroid tissue from stem cells could allow the treatment of patients, which suffer from thyroid hormone deficiency due to defective function, or abnormal development of the thyroid gland. The team of Sabine Costagliola at the IRIBHM (Universit Libre de Bruxelles) recently developed a protocol that allowed for the first time the efficient generation of functional thyroid tissue from stem cells in mice and published the results of their studies in the scientific journal Nature.

Thyroid hormones are a class of iodide-containing molecules that play a critical role in the regulation of various body function including growth, metabolism and heart function and that are crucial for normal brain development. The thyroid gland, an endocrine organ that has been specialized in trapping iodide, is the only organ where these hormones are produced. It is, however, of note that one out of 3000 human newborns is born with congenital hypothyroidism, a condition characterized by insufficient production of thyroid hormones. In the absence of a medical treatment with thyroid hormones -- initiated during the first days after birth -- the child will be affected by an irreversible mental retardation. Moreover, a life-long hormonal treatment is necessary in order to maintain proper regulation of growth and general metabolism.

By employing a protocol in which two important genes can be transiently induced in undifferentiated stem cells, the researchers at IRIBHM were able to efficiently push the differentiation of stem cells into thyrocytes, the primary cell type responsible for thyroid hormone production in the thyroid gland.

A first exciting finding of these studies was the development of functional thyroid tissue already within the culture dishes. As a next step, the team of Sabine Costagliola transplanted the stem-cell-derived thyrocytes into mice lacking a functional thyroid gland. Four weeks after transplantation, the researchers observed that transplanted mice had re-established normal levels of thyroid hormones in their blood and were rescued from the symptoms associated with thyroid hormone deficiency. These findings have several important implications. First, the cell system employed by the IRIBHM group provides a vital tool to better characterize the molecular processes associated with embryonic thyroid development. Second, the results of the transplantation studies open new avenues for the treatment of thyroid hormone deficiency but also for the replacement of thyroid tissue in patients suffering from thyroid cancer.

The researchers are currently developing a similar protocol based on human stem cells and explore ways to generate functional human thyroid tissue by reprogramming pluripotent stem cells (iPS) derived from skin cells.

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The above story is reprinted from materials provided by Universit Libre de Bruxelles, via AlphaGalileo.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Generation of functional thyroid tissue from stem cells

Friday, Oct. 12, 2012

Stem cells derived from a mouse's skin won Shinya Yamanaka the Nobel Prize in physiology or medicine on Monday. Now researchers in Japan are seeking to use his pioneering technology for an even greater prize: restoring sight.

Scientists at the Riken Center for Developmental Biology in Kobe plan to use induced pluripotent stem (iPS) cells in a human trial using patients with macular degeneration, a disease in which the retina becomes damaged and results in loss of vision, Yamanaka, a Kyoto University professor, told reporters the same day in San Francisco.

Companies including Pfizer Inc. are already planning trials of stem cells derived from human embryos, but Riken's will be the first to use a technology that mimics the power of embryonic cells while avoiding the ethical controversy that accompanies them.

"The work in that area looks very encouraging," John B. Gurdon, 79, a professor at the University of Cambridge who shared this year's Nobel Prize with Yamanaka, said in an interview in London.

Yamanaka and Gurdon split the 8 million Swedish kronor (about 94 million) award for experiments 50 years apart demonstrating that mature cells in latent form retain all of the DNA they had as immature stem cells, and that they can be returned to that potent state.

Their findings offer the potential for a new generation of therapies against hard-to-treat diseases like macular degeneration.

In a study published in 1962, Gurdon took a cell from a tadpole's gut, extracted the nucleus and inserted it into the egg cell of an adult frog whose own nucleus had been removed. The reprogrammed egg cell developed into a tadpole with the genetic characteristics of the original tadpole, and subsequent trials yielded adult frogs.

Yamanaka, 50, built on Gurdon's work by adding four genes to a skin cell from a mouse, returning it to its immature state as a stem cell with the potential to become any cell in the body.

He dubbed them induced pluripotent stem cells.

See original here:
Riken to test iPS cells in human trial

STOCKHOLM (Reuters) - A British and a Japanese scientist won the Nobel Prize for Medicine on Monday for work on creating stem cells, opening the door to new methods to diagnose and treat diseases.

Briton John Gurdon and Japan's Shinya Yamanaka equally share the prize of 8 million crowns ($1.2 million), the Nobel Assembly at Sweden's Karolinska Institute said in a statement.

"These groundbreaking discoveries have completely changed our view of the development and specialization of cells."

The discovery offered a new way to create stem cells with the ability to become different types of tissue by effectively turning back the clock on adult cells, restoring them to a so-called "pluripotent" state.

The practical result can be that skin cells can be obtained from ill people to find out more about their diseases and develop new therapies.

Medicine is the first of the Nobel prizes awarded each year. Prizes for achievements in science, literature and peace were first awarded in 1901 in accordance with the will of dynamite inventor and businessman Alfred Nobel. ($1 = 6.5846 Swedish crowns)

(Editing by Patrick Lannin, Alistair Scrutton and Mark Heinrich)

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Japanese, UK scientists win Nobel medicine prize for work with stem cells

A Japanese and a British scientist were awarded the 2012 Nobel Prize in physiology or medicine Monday for their groundbreaking work in turning adult cells into immature ones that might be tweaked further to treat a wide spectrum of diseases. Such research is being aggressively pursued at scientific institutions across San Diego County.

Shinya Yamanaka of Japan and John Gurdon of Great Britain showed that it is possible to alter adult cells to the point where they are very similar to human embryonic stem cells. But the process does not involved the destruction of embryos.

In essence, scientists can now take cells from, say, a person's skin and turn back the clock, making the cell essentially act as though it were new.

The Nobel Assembly at the Karolinska Institute issued a statement today saying, "These groundbreaking discoveries have completely changed our view of the development and cellular specialisation. We now understand that the mature cell does not have to be confined forever to its specialised state. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.

"The discoveries of Gurdon and Yamanaka have shown that specialised cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modifications are not irreversible. We have obtained a new view of the development of cells and organisms.

"Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells.

"For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies."

Gurdon -- who was working in his lab today when he learned that he'd won a Nobel -- made the initial breakthrough about 50 years ago, and Yamanaka built on that work, accelerating the process through genetic engineering.

The Sanford-Burnham Medical Research Institute was created in La Jolla, in part, to probe exactly this area of research.

Will La Jolla scientists win this year's Nobel Prizes?

Link:
Nobel Prize awarded for work on stem cells

Imagine the horror of a soldier losing a limb on the battlefield, or a loved one having a body part amputated due to diabetes. But, what if they could restore their limbs by activating their stem cells?

New Mexico State University biologist Graciela Unguez and a team of researchers found that electric fish, a vertebrate animal just like humans, can regenerate their tails following amputation after activating their stem cells. The findings were published in the May 2012 edition of the scientific journal, PLOS One.

"What's surprising is that as humans, we're one of the few animal species that do not readily regenerate limbs, organs or most tissues," Unguez said. "So, there's a lot of interest in how these fish do it, and what's preventing us from doing it."

Regeneration is the process of restoring lost cells, tissues or organs. According to Unguez, most animals have the ability to regenerate eyes and tails and some animals may be able to regenerate up to half of their bodies.

The researchers discovered that when they cut off up to one third of an electric fish's tail, including the spinal cord, vertebrae, muscles, skin, connective tissues and nerves, the fish would regenerate it. Unguez said the more tissue cut off, the longer the regeneration takes, but for the purpose of her study, it takes about three weeks.

"It's really exciting to us because, here's an example of an animal that can regenerate a lot of tissue types that are also found in humans," Unguez said. "So it puts into question this previous idea that those animals that can regenerate losses of many tissues do it because they do it differently than humans."

Unguez has used the electric fish as a model system to investigate the role that the nervous system plays in the fate of electrically excitable cells like muscle cells for 15 years. She noted that for many years, scientists have thought that highly regenerative animals use a mechanism of regeneration that does not involve stem cells, and this stem cell-based mechanism is well known in humans. In contrast, the stem cell-independent mechanism found in highly regenerative animals is not normally active in humans.

Unguez explained that stem cells are a small population of cells that do not mature and stay with us throughout our life, and then when called upon, they reenter the cell cycle to become muscle cells, neurons, skill cells and such.

But, what Unguez and her collaborators discovered was the opposite. The electric fish actually activated its own muscle and electric organ stem cells to regenerate. She said the adult fish regenerated unendingly with the activation of their stem cells.

"It does not negate other mechanisms, but it definitely showed that it was largely due to an activation of stem cells, just like humans have," Unguez said. "So maybe it's not as far apart, maybe some of the mechanisms involved or the events that need to be activated are more closely related than we thought."

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Electric fish at NMSU activate stem cells for regeneration

Reuters

This undated handout photo shows iPS cells derived from adult human dermal fibroblasts released by Kyoto University Professor Shinya Yamanaka at Center for iPS Cell Research and Application of Kyoto University in Kyoto, western Japan.

By Reuters

Scientists from Britain and Japan shared a Nobel Prize on Monday for the discovery that adult cells can be transformed back into embryo-like stem cells that may one day regrow tissue in damaged brains, hearts or other organs.

John Gurdon, 79, of the Gurdon Institute in Cambridge, Britain and Shinya Yamanaka, 50, of Kyoto University in Japan, discovered ways to create tissue that would act like embryonic cells, without the need to harvest embryos.

They share the $1.2 million Nobel Prize for Medicine, for work Gurdon began 50 years ago and Yamanaka capped with a 2006 experiment that transformed the field of "regenerative medicine" - the field of curing disease by regrowing healthy tissue.

"These groundbreaking discoveries have completely changed our view of the development and specialization of cells," the Nobel Assembly at Stockholm's Karolinska Institute said.

Photoblog: Click for a close-up viiew of the Nobel Prize-winning stem cell research

All of the body's tissue starts as stem cells, before developing into skin, blood, nerves, muscle and bone. The big hope for stem cells is that they can be used to replace damaged tissue in everything from spinal cord injuries to Parkinson's disease.

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Nobel Prize awarded for stem cell breakthroughs

Shinya Yamanaka MD, PhD

Here are answers to frequently asked questions about induced pluripotent stem cells, or iPS cells, the type of cell that has been reprogrammed from an adult cell, such as a skin or blood cell.

What are induced pluripotent stem cells?

Induced pluripotent stem cells, or iPS cells, are a type of cell that has been reprogrammed from an adult cell, such as a skin or blood cell. iPS cells are pluripotent cells because, like embryonic stem cells, they can develop into virtually any type of cell. iPS cells are distinct from embryonic stem cells, however, because they are derived from adult tissue, rather than from embryos. iPS cells are also distinct from adult stem cells, which naturally occur in small numbers in thehuman body.

In 2006, Shinya Yamanaka developed the method for inducing skin cells from mice into becoming like pluripotent stem cells and called them iPS cells. In 2007, Yamanaka did the same with adult human skin cells.

Yamanakas experiments revealed that adult skin cells, when treated with four pieces of DNA (now called the Yamanaka factors), can induce skin cells to revert back to their pluripotent state. His discovery has since led to a variety of methods for reprogramming adult cells into stem cells that can become virtually any cell type such as a beating heart cell or a neuron that can transmit chemical signals in the brain. This allows researchers to create patient-specific celllines that can be studied and used in everything from drug therapies to regenerative medicine.

How are iPS cells different from embryonic stem cells?

iPS cells are a promising alternative to embryonic stem cells. Embryonic stem cells hold tremendous potential for regenerative medicine, in which damaged organs and tissues could be replaced or repaired. But the use of embryonic stem cells has long been controversial. iPS cells hold the same sort of promise but avoid controversy because they do not require the destruction of human embryos. Nor do they require the harvesting of adult stem cells. Rather, they simply require a small tissue sample from a living human.

Why is iPS cell technology so important?

In addition to avoiding the controversial use of embryonic stem cells, iPS cell technology also represents an entirely new platform for fundamental studies of human disease. Rather than using models made in yeast, flies or mice for disease research, iPS cell technology allows human stem cells to be created from patients with a specific disease. As a result, the iPS cells contain a complete set of the genes that resulted in that disease and thus represent the potential of a farsuperior human model for studying disease and testing new drugs and treatments. In the future, iPS cells could be used in a Petri dish to test both drug safety andefficacy for an individual patient.

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Stem Cell Science Q & A

STOCKHOLM (Reuters) - Scientists from Britain and Japan shared a Nobel Prize on Monday for the discovery that adult cells can be transformed back into embryo-like stem cells that may one day regrow tissue in damaged brains, hearts or other organs.

John Gurdon, 79, of the Gurdon Institute in Cambridge, Britain and Shinya Yamanaka, 50, of Kyoto University in Japan, discovered ways to create tissue that would act like embryonic cells, without the need to collect the cells from embryos.

They share the $1.2 million Nobel Prize for Medicine, for work Gurdon began 50 years ago and Yamanaka capped with a 2006 experiment that transformed the field of "regenerative medicine" - the search for ways to cure disease by growing healthy tissue.

"These groundbreaking discoveries have completely changed our view of the development and specialisation of cells," the Nobel Assembly at Stockholm's Karolinska Institute said.

All of the body starts as stem cells, before developing into tissue like skin, blood, nerves, muscle and bone. The big hope is that stem cells can grow to replace damaged tissue in cases from spinal cord injuries to Parkinson's disease.

Scientists once thought it was impossible to turn adult tissue back into stem cells. That meant new stem cells could only be created by taking them from embryos, which raised ethical objections that led to research bans in some countries.

As far back as 1962 Gurdon became the first scientist to clone an animal, making a healthy tadpole from the egg of a frog with DNA from another tadpole's intestinal cell. That showed that developed cells carry the information to make every cell in the body - decades before other scientists made world headlines by cloning the first mammal from adult DNA, Dolly the sheep.

More than 40 years later, Yamanaka produced mouse stem cells from adult mouse skin cells by inserting a small number of genes. His breakthrough effectively showed that the development that takes place in adult tissue could be reversed, turning adult tissue back into cells that behave like embryos.

Stem cells created from adult tissue are known as "induced pluripotency stem cells", or iPS cells. Because patients may one day be treated with stem cells from their own tissue, their bodies might be less likely to reject them.

"The eventual aim is to provide replacement cells of all kinds," Gurdon's institute explains on its website.

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UK, Japan scientists win Nobel for adult stem cell discovery

AFP/Getty Images

John B. Gurdon (left) and Shinya Yamanaka will share the prize, worth about $1.2 million.

The two scientists who won this year's Nobel Prize in Physiology or Medicine discovered that cells in our body have the remarkable ability to reinvent themselves. They found that every cell in the human body, from our skin and bones to our heart and brain, can be coaxed into forming any other cell.

The process is called reprogramming, and its potential for new drugs and therapies is vast. If neurons or heart cells are damaged by disease or aging, then cells from the skin or blood potentially could be induced to reprogram themselves and repair the damaged tissue.

The winners John Gurdon of the Gurdon Institute in Cambridge, England, and Shinya Yamanaka of Kyoto University in Japan and the Gladstone Institute in San Francisco made their discoveries more than 40 years apart.

In 1962, Gurdon proved that a cell from a frog's stomach contained the entire blueprint to make a whole frog. When he took the cell's nucleus and popped it into a frog egg, the egg developed into a normal frog.

This method eventually was used to clone all sorts of animals, including cats, dogs, horses and, most famously, Dolly the sheep the first mammal cloned from an adult cell. Gurdon, 79, continues to study reprogramming and was working in his lab when he received the call from the Nobel committee.

But a major obstacle stood in the way of further development of these stem cells: Getting the frog's stomach cell to strip away its specialization and turn into one of the 200 or so cell types known to exist in animals always required the use of an egg.

A question hung over the field for decades: Could a specialized cell reprogram itself all on its own?

In 2006, Yamanaka and graduate student Kazutoshi Takahashi found the answer, and it sent shockwaves through biology and medicine. They demonstrated that any cell could be reset and induced to develop into another cell type. And, even more remarkably, that it took little to get the job done.

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Nobel Winners Unlocked Cells' Unlimited Potential

STOCKHOLM - Scientists from Britain and Japan shared a Nobel Prize on Monday for the discovery that adult cells can be transformed back into embryo-like stem cells that may one day regrow tissue in damaged brains, hearts or other organs.

John Gurdon, 79, of the Gurdon Institute in Cambridge, Britain and Shinya Yamanaka, 50, of Kyoto University in Japan, discovered ways to create tissue that would act like embryonic cells, without the need to harvest embryos.

They share the $1.2 million Nobel Prize for Medicine, for work Gurdon began 50 years ago and Yamanaka capped with a 2006 experiment that transformed the field of "regenerative medicine" - the field of curing disease by regrowing healthy tissue.

"These groundbreaking discoveries have completely changed our view of the development and specialization of cells," the Nobel Assembly at Stockholm's Karolinska Institute said.

All of the body's tissue starts as stem cells, before developing into skin, blood, nerves, muscle and bone. The big hope for stem cells is that they can be used to replace damaged tissue in everything from spinal cord injuries to Parkinson's disease.

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UK, Japan scientists win Nobel for stem cell breakthroughs