London, October 5 (ANI): Using stem cells made from skin, a Japanese team has created healthy eggs that, once fertilised, grow into normal baby mice.

These babies later had their own babies, the BBC reported.

The team at Kyoto University used stem cells from two sources: those collected from an embryo and skin-like cells, which were reprogrammed, into becoming stem cells.

The first step was to turn the stem cells into early versions of eggs.

A "reconstituted ovary" was then built by surrounding the early eggs with other types of supporting cells that are normally found in an ovary. This was transplanted into female mice. Surrounding the eggs in this environment helped them to mature.

IVF techniques were used to collect the eggs, fertilise them with sperm from a male mouse and implant the fertilised egg into a surrogate mother.

"They develop to be healthy and fertile offspring," Dr Katsuhiko Hayashi, from Kyoto University, told the BBC.

Those babies then had babies of their own, whose "grandmother" was a cell in a laboratory dish.

If the same methods could be used in people then, it could help infertile couples have children and even allow women to overcome the menopause.

But experts say many scientific and ethical hurdles must be overcome before the technique could be adapted for people.

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Life created for first time from eggs made from skin cells

Professor Robert Norman, Professor of Reproductive Medicine at the University of Adelaide in Australia, said: "While this is a major contribution to knowledge, application to humans is still a long way off but for the first time the goal appears to be in sight.

In the new study, the scientists transformed skin cells into personalised stem cells, which were then fertilised via IVF and ultimately resulted in three fertile baby mice.

Safety concerns must be addressed, particularly into the long-term health of the resulting offspring, before researchers come any closer to determining whether the treatment could be viable in humans.

The researchers wrote in the latest online issue of the journal Science: "Our system serves as a robust foundation to investigate and further reconstitute female germ line development in vitro (in the laboratory), not only in mice, but also in other mammals, including humans."

Dr Allan Pacey, senior lecturer in reproduction and developmental medicine at the University of Sheffield, said: "What is remarkable about this work is the fact that, although the process is still quite inefficient, the offspring appeared healthy and were themselves fertile as adults.

"This is a great step forward, but I would urge caution as this is a laboratory study and we are still quite a long way from clinical trials taking place in humans."

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Eggs created from stem cells in fertility breakthrough

Eggs capable of being fertilised and making babies can be created in the laboratory from skin cells, a study has shown.

Scientists successfully produced three fertile baby mice using the technique, which involves transforming ordinary skin cells into personalised stem cells.

The same Japanese team created viable mouse sperm from embryonic stem cells earlier this year.

Together both advances greatly increase the likelihood of radical and controversial future treatments for restoring fertility.

It could mean creating sperm for men whose fertility has been wiped out by cancer therapy, or reversing the menopause in women long after they have used up their natural supply of eggs.

However, many questions about safety and ethics will have to be answered first.

In August, scientists from Kyoto University in Japan announced that they had created sperm cells from mouse embryo stem cells.

Injected into mouse eggs, the sperm produced embryos which developed into healthy baby mice.

The same team, led by Dr Katsuhiko Hayashi, carried out the latest research which focused on eggs rather than sperm.

The scientists mirrored their earlier achievement by transforming stem cells from mouse embryos into eggs which could be fertilised to produce offspring.

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Lab-Made Mouse Eggs Raise Fertility Options

Eggs capable of being fertilised and making babies can be created in the laboratory from skin cells, a study has shown.

Scientists successfully produced three fertile baby mice using the technique, which involves transforming ordinary skin cells into personalised stem cells.

The same Japanese team created viable mouse sperm from embryonic stem cells earlier this year.

Together, both advances greatly increase the likelihood of radical and controversial future treatments for restoring fertility. It could mean creating sperm for men whose fertility has been wiped out by cancer therapy or reversing the menopause in women long after they have used up their natural supply of eggs.

In August, scientists from Kyoto University in Japan announced that they had created sperm cells from mouse embryo stem cells. Injected into mouse eggs, the sperm produced embryos which developed into healthy baby mice.

The same team, led by Dr Katsuhiko Hayashi, carried out the latest research which focused on eggs rather than sperm. The scientists mirrored their earlier achievement by transforming stem cells from mouse embryos into eggs which could be fertilised to produce offspring. But they also took a further step by obtaining mouse pups from eggs derived from ordinary skin cells.

The researchers wrote in the latest online issue of the journal Science: "Our system serves as a robust foundation to investigate and further reconstitute female germline development in vitro (in the laboratory), not only in mice but also in other mammals, including humans."

The "germline" consists of genetic material carried in reproductive cells that can be passed onto future generations.

Dr Allan Pacey, senior lecturer in reproduction and developmental medicine at the University of Sheffield, said: "This is a very technical piece of work which pushes much further the science of how eggs are generated and how we might one day be able to routinely stimulate the new production of eggs for women who are infertile.

"What is remarkable about this work is the fact that, although the process is still quite inefficient, the offspring appeared healthy and were themselves fertile as adults. This is a great step forward but I would urge caution as this is a laboratory study and we are still quite a long way from clinical trials taking place in humans."

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Eggs can be created from skin cells

Mouse pups from induced pluripotent stem cell-derived eggs; image courtesy of Katsuhiko Hayashi

Stem cells have been coaxed into creating everything from liver cells to beating heart tissue. Recently, these versatile cells were even used to make fertile mouse sperm, suggesting that stem cell technology might eventually be able to play a role in the treatment of human infertility.

Now two types of stem cells have been turned into viable mouse egg cells that were fertilized and eventually yielded healthy baby mice. Details of this achievement were published online October 4 in Science.

Mouse oocytes; image courtesy of Katsuhiko Hayashi

Katsuhiko Hayashi, of Kyoto Universitys School of Medicine, were able to create the eggs with embryonic stem cells as well as with induced pluripotent stem cells (formed from adult cells).

The team started with female embryonic stem cells and then coaxed them genetically to revert to an earlier developmental stage (primordial germ cell-like cells). These cells were blended with gonadal somatic cells, important in the development of sexual differentiation, to create reconstituted ovaries. The researchers then transplanted these cultured assemblages into female mice (in either the actual ovary or the kidney) for safekeeping and to allow the stem cells to mature into oocytes in a natural environment.

Healthy adult mice from litter produced from induced pluripotent stem cell-based oocytes; image courtesy of Katsuhiko Hayashi

To test the eggs fertility, the new oocytes were removed from the mice for an in vitro fertilization with mouse spermand then re-implanted into the female mice. The experimental females went on to bear normally developing and fertile offspring. The procedure was then also performed successfully with induced pluripotent stem cells from adult skin cells with similar results.

Our system serves as a robust foundation to investigate and further reconstitute female germline development in vitro, the researchers noted in their paper, not only in mice, but also in other mammals, including humans.

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Baby Mice Born from Eggs Made from Stem Cells

4 October 2012 Last updated at 18:31 ET By James Gallagher Health and science reporter, BBC News

Stem cells made from skin have become "grandparents" after generations of life were created in experiments by scientists in Japan.

The cells were used to create eggs, which were fertilised to produce baby mice. These later had their own babies.

If the technique could be adapted for people, it could help infertile couples have children and even allow women to overcome the menopause.

But experts say many scientific and ethical hurdles must be overcome.

Stem cells are able to become any other type of cell in the body from blood to bone, nerves to skin.

Last year the team at Kyoto University managed to make viable sperm from stem cells. Now they have performed a similar feat with eggs.

They used stem cells from two sources: those collected from an embryo and skin-like cells which were reprogrammed into becoming stem cells.

I just thought wow! The science is quite brilliant

The first step, reported in the journal Science, was to turn the stem cells into early versions of eggs.

See the article here:
Skin cells become 'grandparents'

Washington, October 2 (ANI): A new study has suggested that induced pluripotent stem (iPS) cells - which are derived from adult human skin cells but have embryonic properties - could soon be used to restore vision in people with macular degeneration and other diseases that affect the eye's retina.

In the study conducted by Columbia ophthalmologists and stem cell researchers, adult stem cells developed from a patient's skin cells improved the vision of blind mice.

"With eye diseases, I think we're getting close to a scenario where a patient's own skin cells are used to replace retina cells destroyed by disease or degeneration," said the study's principal investigator, Stephen Tsang, MD, PhD, associate professor of ophthalmology and pathology and cell biology.

"It's often said that iPS transplantation will be important in the practice of medicine in some distant future, but our paper suggests the future is almost here," he stated.

The advent of human iPS cells in 2007 was greeted with excitement from scientists who hailed the development as a way to avoid the ethical complications of embryonic stem cells and create patient-specific stem cells.

Like embryonic stem cells, iPS cells can develop into any type of cell. Thousands of different iPS cell lines from patients and healthy donors have been created in the last few years, but they are almost always used in research or drug screening.

In Tsang's new preclinical iPS study, human iPS cells - derived from the skin cells of a 53-year-old donor - were first transformed with a cocktail of growth factors into cells in the retina that lie underneath the eye's light-sensing cells.

The primary job of the retina cells is to nourish the light-sensing cells and protect the fragile cells from excess light, heat, and cellular debris. If the retina cells die - which happens in macular degeneration and retinitis pigmentosa - the photoreceptor cells degenerate and the patient loses vision.

Macular degeneration is a leading cause of vision loss in the elderly, and it is estimated that 30 percent of people will have some form of macular degeneration by age 75.

In their study, the researchers injected the iPS-derived retina cells into the right eyes of 34 mice that had a genetic mutation that caused their retina cells to degenerate.

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Patients' own skin cells could restore vision in elderly with macular degeneration

Newswise An experimental treatment for blindness, developed from a patients skin cells, improved the vision of blind mice in a study conducted by Columbia ophthalmologists and stem cell researchers.

The findings suggest that induced pluripotent stem (iPS) cells which are derived from adult human skin cells but have embryonic properties could soon be used to restore vision in people with macular degeneration and other diseases that affect the eyes retina.

With eye diseases, I think were getting close to a scenario where a patients own skin cells are used to replace retina cells destroyed by disease or degeneration, says the studys principal investigator, Stephen Tsang, MD, PhD, associate professor of ophthalmology and pathology & cell biology. Its often said that iPS transplantation will be important in the practice of medicine in some distant future, but our paper suggests the future is almost here.

The advent of human iPS cells in 2007 was greeted with excitement from scientists who hailed the development as a way to avoid the ethical complications of embryonic stem cells and create patient-specific stem cells. Like embryonic stem cells, iPS cells can develop into any type of cell. Thousands of different iPS cell lines from patients and healthy donors have been created in the last few years, but they are almost always used in research or drug screening.

No iPS cells have been transplanted into people, but many ophthalmologists say the eye is the ideal testing ground for iPS therapies.

The eye is a transparent and accessible part of the central nervous system, and thats a big advantage. We can put cells into the eye and monitor them every day with routine non-invasive clinical exams, Tsang says. And in the event of serious complications, removing the eye is not a life-threatening event.

In Tsangs new preclinical iPS study, human iPS cells derived from the skin cells of a 53-year-old donor were first transformed with a cocktail of growth factors into cells in the retina that lie underneath the eyes light-sensing cells.

The primary job of the retina cells is to nourish the light-sensing cells and protect the fragile cells from excess light, heat, and cellular debris. If the retina cells die which happens in macular degeneration and retinitis pigmentosa the photoreceptor cells degenerate and the patient loses vision. Macular degeneration is a leading cause of vision loss in the elderly, and it is estimated that 30 percent of people will have some form of macular degeneration by age 75. Macular degeneration currently affects 7 million Americans and its incidence is expected to double by 2020.

In their study, the researchers injected the iPS-derived retina cells into the right eyes of 34 mice that had a genetic mutation that caused their retina cells to degenerate.

In many animals, the human cells assimilated into mouse retina without disruption and functioned as normal retina cells well into the animals old age. Control mice that got injections of saline or inactive cells showed no improvement in retina tests.

Go here to read the rest:
Stem Cells Improve Visual Function in Blind Mice

ScienceDaily (Sep. 25, 2012) The process researchers use to generate induced pluripotent stem cells (iPSCs) -- a special type of stem cell that can be made in the lab from any type of adult cell -- is time consuming and inefficient. To speed things up, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) turned to kinase inhibitors. These chemical compounds block the activity of kinases, enzymes responsible for many aspects of cellular communication, survival, and growth.

As they outline in a paper published September 25 in Nature Communications, the team found several kinase inhibitors that, when added to starter cells, help generate many more iPSCs than the standard method. This new capability will likely speed up research in many fields, better enabling scientists around the world to study human disease and develop new treatments.

"Generating iPSCs depends on the regulation of communication networks within cells," explained Tariq Rana, Ph.D., program director in Sanford-Burnham's Sanford Children's Health Research Center and senior author of the study. "So, when you start manipulating which genes are turned on or off in cells to create pluripotent stem cells, you are probably activating a large number of kinases. Since many of these active kinases are likely inhibiting the conversion to iPSCs, it made sense to us that adding inhibitors might lower the barrier."

According to Tony Hunter, Ph.D., professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and director of the Salk Institute Cancer Center, "The identification of small molecules that improve the efficiency of generating iPSCs is an important step forward in being able to use these cells therapeutically. Tariq Rana's exciting new work has uncovered a class of protein kinase inhibitors that override the normal barriers to efficient iPSC formation, and these inhibitors should prove useful in generating iPSCs from new sources for experimental and ultimately therapeutic purposes." Hunter, a kinase expert, was not involved in this study.

The promise of iPSCs

At the moment, the only treatment option available to many heart failure patients is a heart transplant. Looking for a better alternative, many researchers are coaxing stem cells into new heart muscle. In Alzheimer's disease, researchers are also interested in stem cells, using them to reproduce a person's own malfunctioning brain cells in a dish, where they can be used to test therapeutic drugs. But where do these stem cells come from? Since the advent of iPSC technology, the answer in many cases is the lab. Like their embryonic cousins, iPSCs can be used to generate just about any cell type -- heart, brain, or muscle, to name a few -- that can be used to test new therapies or potentially to replace diseased or damaged tissue.

It sounds simple enough: you start with any type of differentiated cell, such as skin cells, add four molecules that reprogram the cells' genomes, and then try to catch those that successfully revert to unspecialized iPSCs. But the process takes a long time and isn't very efficient -- you can start with thousands of skin cells and end up with just a few iPSCs.

Inhibiting kinases to make more iPSCs

Zhonghan Li, a graduate student in Rana's laboratory, took on the task of finding kinase inhibitors that might speed up the iPSC-generating process. Scientists in the Conrad Prebys Center for Chemical Genomics, Sanford-Burnham's drug discovery facility, provided Li with a collection of more than 240 chemical compounds that inhibit kinases. Li painstakingly added them one-by-one to his cells and waited to see what happened. Several kinase inhibitors produced many more iPSCs than the untreated cells -- in some cases too many iPSCs for the tiny dish housing them. The most potent inhibitors targeted three kinases in particular: AurkA, P38, and IP3K.

Working with the staff in Sanford-Burnham's genomics, bioinformatics, animal modeling, and histology core facilities -- valuable resources and expertise available to all Sanford-Burnham scientists and the scientific community at large -- Rana and Li further confirmed the specificity of their findings and even nailed down the mechanism behind one inhibitor's beneficial actions.

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Making it easier to make stem cells: Kinase inhibitors lower barrier to producing stem cells in lab

Public release date: 25-Sep-2012 [ | E-mail | Share ]

Contact: Heather Buschman hbuschman@sanfordburnham.org 858-795-5343 Sanford-Burnham Medical Research Institute

LA JOLLA, Calif., September 25, 2012 The process researchers use to generate induced pluripotent stem cells (iPSCs)a special type of stem cell that can be made in the lab from any type of adult cellis time consuming and inefficient. To speed things up, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) turned to kinase inhibitors. These chemical compounds block the activity of kinases, enzymes responsible for many aspects of cellular communication, survival, and growth. As they outline in a paper published September 25 in Nature Communications, the team found several kinase inhibitors that, when added to starter cells, help generate many more iPSCs than the standard method. This new capability will likely speed up research in many fields, better enabling scientists around the world to study human disease and develop new treatments.

"Generating iPSCs depends on the regulation of communication networks within cells," explained Tariq Rana, Ph.D., program director in Sanford-Burnham's Sanford Children's Health Research Center and senior author of the study. "So, when you start manipulating which genes are turned on or off in cells to create pluripotent stem cells, you are probably activating a large number of kinases. Since many of these active kinases are likely inhibiting the conversion to iPSCs, it made sense to us that adding inhibitors might lower the barrier."

According to Tony Hunter, Ph.D., professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and director of the Salk Institute Cancer Center, "The identification of small molecules that improve the efficiency of generating iPSCs is an important step forward in being able to use these cells therapeutically. Tariq Rana's exciting new work has uncovered a class of protein kinase inhibitors that override the normal barriers to efficient iPSC formation, and these inhibitors should prove useful in generating iPSCs from new sources for experimental and ultimately therapeutic purposes." Hunter, a kinase expert, was not involved in this study.

The promise of iPSCs

At the moment, the only treatment option available to many heart failure patients is a heart transplant. Looking for a better alternative, many researchers are coaxing stem cells into new heart muscle. In Alzheimer's disease, researchers are also interested in stem cells, using them to reproduce a person's own malfunctioning brain cells in a dish, where they can be used to test therapeutic drugs. But where do these stem cells come from? Since the advent of iPSC technology, the answer in many cases is the lab. Like their embryonic cousins, iPSCs can be used to generate just about any cell typeheart, brain, or muscle, to name a fewthat can be used to test new therapies or potentially to replace diseased or damaged tissue.

It sounds simple enough: you start with any type of differentiated cell, such as skin cells, add four molecules that reprogram the cells' genomes, and then try to catch those that successfully revert to unspecialized iPSCs. But the process takes a long time and isn't very efficientyou can start with thousands of skin cells and end up with just a few iPSCs.

Inhibiting kinases to make more iPSCs

Zhonghan Li, a graduate student in Rana's laboratory, took on the task of finding kinase inhibitors that might speed up the iPSC-generating process. Scientists in the Conrad Prebys Center for Chemical Genomics, Sanford-Burnham's drug discovery facility, provided Li with a collection of more than 240 chemical compounds that inhibit kinases. Li painstakingly added them one-by-one to his cells and waited to see what happened. Several kinase inhibitors produced many more iPSCs than the untreated cellsin some cases too many iPSCs for the tiny dish housing them. The most potent inhibitors targeted three kinases in particular: AurkA, P38, and IP3K.

See more here:
Making it easier to make stem cells

SHANGHAI doctors announced the success of a novel technology that uses people's own skin via stem cells to grow a new face for seriously disfigured patients.

It's an alternative to the surgery used in the West in which doctors transplant the face from a dead body to a patient.

Facial tissue developed with the new technology is more readily accepted physically and psychologically by patients and has no ethical issues, doctors from Shanghai No. 9 People's Hospital said yesterday.

Since adopting the new technology, doctors have used it on more than 60 patients, including seven who needed their whole face replaced or major facial changes.

Of the seven, six were a success, while one case failed as skin on part of the face died, doctors said.

Patients include women disfigured by having sulfuric acid splashed in their faces, people who lost their nose during a fight and a person whose face was seriously burned in a fire.

Under the technology, doctors remove certain blood vessels from the patient's leg to build a small vessel net and transplant it into a place on the body to grow the new face, usually on the a patient's upper chest.

Then doctors use a skin dilator to expand the skin like a bulging ball. Later they inject the patient's own stem cells to help the skin grow stronger and stimulate the growth of blood vessels.

Soft bones which are shaped into facial features like a nose and upper jaw bone in line with the patient's own facial skeleton are then transplanted under the new facial skin.

Finally, the new face is transplanted onto the disfigured face. The new face, which is thin and comprised of a whole piece of living skin, will join with the facial muscles, thus giving a patient natural facial expressions and function to the greatest extent possible.

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Eastday-Shanghai doctors reveal face-change leap

TORONTO, Sept. 10, 2012 /CNW/ - Sigmacon Skin Sciences announced it is the exclusive Canadian distributor of Stemulation, a luxury skin care line that uses the healing power of human stem cells to combat wrinkles and other signs of aging.

Stemulation is based on the science that stem cells can be effectively used for skin rejuvenation, tissue repair and wound healing. A research team of specialists spent two years capturing growth factors from adult human skin cells, which they turned into an active ingredient and the basis for Stemulation products. These growth factors stimulate collagen and the reproduction of new skin cells to reduce wrinkles, eliminate sun spots and smooth scars and fine lines. It truly is a groundbreaking (and technology-backed) new way to achieve younger-looking skin!

The Stemulation line includes a serum, cleanser, exfoliant and face and body creams. The line will be sold through select doctors, estheticians and medical spas.

ABOUT Sigmacon Skin Sciences is the national distributor of a comprehensive set of performance skin care products with dedicated product specialists and trainings all across Canada. Our product lines include professional treatments, sun protection products and results-oriented home care. Sigmacon is also the distributor of advanced medical and aesthetic devices. Visit http://www.skinsciences.ca to learn more.

Image with caption: "The Future of Skin Care: Stemulation Facial Serum and Boost Crme used over 1 year. (CNW Group/Sigmacon Skin Sciences)". Image available at: http://photos.newswire.ca/images/download/20120910_C3135_PHOTO_EN_17420.jpg

The rest is here:
Introducing Canadians to a whole new way to treat aging skin: Stemulation

Scientists have for the first time watched and manipulated stem cells as they regenerate tissue in an uninjured mammal, Yale researchers report July 1 online in the journal Nature.

Using a sophisticated imaging technique, the researchers also demonstrated that mice lacking a certain type of cell do not regrow hair. The same technique could shed light on how stem cells interact with other cells and trigger repairs in a variety of other organs, including lung and heart tissue.

This tells us a lot about how the tissue regeneration process works, said Valentina Greco, assistant professor of genetics and of dermatology at the Yale Stem Cell Center, researcher for the Yale Cancer Center and senior author of the study.

Greco and her team focused on stem cell behavior in the hair follicle of the mouse. The accessibility of the hair follicle allowed real-time and non-invasive imaging through a technology called 2-photon intravital microscopy.

Using this method, Panteleimon Rompolas, a post-doctoral fellow in Grecos lab and lead author of this paper, was able to study the interaction between stem cells and their progeny, which produce all the different types of cells in the tissue. The interaction of these cells with the immediate environment determines how cells divide, where they migrate and which specialized cells they become.

The technology allowed the team to discover that hair growth in mice cannot take place in the absence of connective tissue called mesenchyme, which appears early in embryonic development.

Stem cells not only spur growth of hair in mammals including humans, but also can serve to regenerate many other types of tissues.

Understanding how stem cell behavior is regulated by the microenvironment can advance our use of stem cells for therapeutic purposes and uncover mechanisms that go wrong in cancer and other diseases, Greco said.

The study was funded by an Alexander Brown Coxe postdoctoral fellowship. This work was supported in part by the American Skin Association and the American Cancer Society and the Yale Rheumatologic Disease Research Core Center and the National Institutes of Health.

Other Yale authors include Elizabeth Deschene, Giovanni Zito, David G. Gonzalez, Ichiko Saotome and Ann M. Haberman.

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In real time, Yale scientists watch stem cells at work regenerating tissue

Editor's Choice Main Category: Huntingtons Disease Also Included In: Stem Cell Research;Neurology / Neuroscience Article Date: 29 Jun 2012 - 14:00 PDT

Current ratings for: Brain Cells Derived From Skin Cells For Huntington's Research

3 (1 votes)

At present, there is no cure for the disease and no treatments are available. These findings open up the possibility of testing treatments for the deadly disorder in a petri dish.

The study is the work of a Huntington's Disease iPSC Consortium, including researchers from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, and six other groups.

Huntington's disease is an inherited, deadly neurodegenerative disorder. The onset of HD generally occurs during midlife, although it can also strike in childhood - as in the patient who donated the material for the cells generated in this study. The disease causes jerky, twitch-like movements, lack of muscle control, psychiatric disorders and dementia, and ultimately death.

Christopher A. Ross, M.D., Ph.D., a professor of psychiatry and behavioral sciences, neurology, pharmacology and neuroscience at the Johns Hopkins University School of Medicine and one of the lead researchers of the study, explained:

The team are currently testing small molecules for the ability to block HP iPSC degeneration. According to the researchers, these molecules could potentially be developed into new drugs for Huntington's disease.

Furthermore, the teams ability to create "HD in a dish" may also have implications for similar research in other diseases such as Parkinson's and Alzheimer's.

In the study, the team took a skin biopsy from a 7-year-old patient with very early onset of severe HD. In the laboratory of Hongjun Song, Ph.D., a professor at Johns Hopkins' Institute for Cell Engineering, the skin cells were grown in culture and then created into pluripotent stem cells. In addition, a second cell line was created in the same way in Dr. Ross's lab from an individuals without HD.Simultaneously, other HD and control iPS cell lines were generated as part of the NINDS funded HD iPS cell consortium.

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Brain Cells Derived From Skin Cells For Huntington's Research

June 29, 2012

Connie K. Ho for redOrbit.com Your Universe Online

In 1993, the autosomal dominant gene mutation responsible for Huntingtons Disease (HD) was discovered. However, no treatments are known to slow its progression. New research may pave the way to better understanding of the disease. Researchers at Johns Hopkins recently announced that they were able to produce stem cells from skin cells from a person who had severe, early-onset form of HD; the cells were then changed into neurons that degenerated like the cells affected by HD.

The research was recently published in the journal Cell Stem Cell. The investigators worked with an international consortium in creating HD in a dish. The group was made up of scientists from Johns Hopkins University School of Medicine, Cedars-Sinai Medical Center, the University of California at Irvine, as well as six other groups. The team looked at many other HD cell lines and control cell lines to verify that the results were consistent and reproducible in other labs. The investigators believe that the findings allow them to better understand and eliminate cells in people in with HD. They hope to study the effects of possible drug treatments on cells that would be otherwise found deep in the brain.

Having these cells will allow us to screen for therapeutics in a way we havent been able to before in Huntingtons disease, remarked lead researcher Dr. Christopher A. Ross, a professor of psychiatry and behavioral sciences, neurology, pharmacology and neuroscience at the Johns Hopkins University School of Medicine, in a prepared statement. For the first time, we will be able to study how drugs work on human HD neurons and hopefully take those findings directly to the clinic.

The team of researchers is studying small molecules for the ability to block HD iPSC degeneration to see if they can be developed into new drugs for HD. As well, the ability to produce from stem cells the same neurons found in HD may have effects for similar research in other neurodegenerative diseases like Alzheimers and Parkinsons. In the experiment, Ross took a skin biopsy from a patient with very early onset HD. The patient was seven years old at the time, with a severe form of disease and a mutation that caused it. By using cells from a patient who had quickly progressing HD, Ross team were able to mimic HD in a way that could be used by patients who had different forms of HD.

The skin cells were grown in culture and reprogrammed to induce stem cells that were pluripotent. Then, another cell line was created in the same way from someone who didnt have HD. The other HD and control iPS cells were produced as part of the NINDS funded HD iPS cell consortium. Investigators from Johns Hopkins and the other consortium labs changed the cells into typical neurons and then into medium spiny neurons. The process took a total of three months and the scientists found the medium spiny neurons from the HD cells acted how the medium spiny neurons form an HD patient would. The cells demonstrated quick degeneration when cultured in the lab with a basic culture medium that didnt include extensive supporting nutrients. On the other hand, control cell lines didnt demonstrate neuronal degeneration.

These HD cells acted just as we were hoping, says Ross, director of the Baltimore Huntingtons Disease Center. A lot of people said, Youll never be able to get a model in a dish of a human neurodegenerative disease like this. Now, we have them where we can really study and manipulate them, and try to cure them of this horrible disease. The fact that we are able to do this at all still amazes us.

Source: Connie K. Ho for redOrbit.com Your Universe Online

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Skin Cells Create Stem Cells In Huntington Disease Study

An international consortium of Huntington's disease experts, including several from the Sue & Bill Gross Stem Cell Research Center at UC Irvine and the UCSF Gladstone Institutes, has generated a human model of the deadly inherited disorder directly from the skin cells of affected patients.

The re-created neurons, which live in a petri dish, will help researchers better understand what disables and kills brain cells in people with HD and let them gauge the effects of potential drug therapies on cells that are otherwise locked deep in the brain.

UCI scientists were part of a consortium that in 1993 identified the autosomal dominant gene mutation responsible for HD, but there is still no cure, and no treatments are available to even slow its onset or progression. The research, published online today in the journal Cell Stem Cell, is the work of the Huntington's Disease iPSC Consortium. Participants examined several other cell lines and control cell lines to ensure that their results were consistent and reproducible in different labs.

"Our discovery will enable us for the first time to test therapies on human Huntington's disease neurons," said Leslie Thompson, UCI professor of psychiatry & human behavior and neurobiology & behavior, one of the world's leading HD experts and a senior author of the study. "This has been a remarkable time in HD research, with the advent of stem cell technologies that have allowed these scientific advancements. Also, having a team of scientists working together as a consortium has benefited the research tremendously and accelerated its pace."

Huntington's is such a rare disease, although it is the most common inherited neurodegenerative disorder. It afflicts approximately 30,000 people in the United States-with another 75,000 people carrying the gene that will eventually lead to it.

"An advantage of this human model is that we now have the ability to identify changes in brain cells over time-during the degeneration process and at specific stages of brain-cell development," said Gladstone Senior Investigator Dr. Steve Finkbeiner. "We hope this model will help us more readily uncover relevant factors that contribute to Huntington's disease and especially to find successful therapeutic approaches."

UC Irvine press release

Gladstone Institutes press release

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Huntington’s disease neurons created from stem cells

Newswise Researchers at the Buck Institute have corrected the genetic mutation responsible for Huntingtons Disease (HD) using a human induced pluripotent stem cell (iPSC) that came from a patient suffering from the incurable, inherited neurodegenerative disorder. Scientists took the diseased iPSCs, made the genetic correction, generated neural stem cells and then transplanted the mutation-free cells into a mouse model of HD where they are generating normal neurons in the area of the brain affected by HD. Results of the research are published in the June 28, 2012 online edition of the journal Cell Stem Cell.

iPSCs are reverse-engineered from human cells such as skin, back to a state where they can be coaxed into becoming any type of cell. They can be used to model numerous human diseases and may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory. We believe the ability to make patient-specific, genetically corrected iPSCs from HD patients is a critical step for the eventual use of these cells in cell replacement therapy, said Buck faculty Lisa Ellerby, PhD, lead author of the study. The genetic correction reversed the signs of disease in these cells the neural stem cells were no longer susceptible to cell death and the function of their mitochondria was normal. Ellerby said the corrected cells could populate the area of the mouse brain affected in HD, therefore, the next stage of research involves transplantation of corrected cells to see if the HD-afflicted mice show improved function. Ellerby said these studies are important as now we can deliver patient-specific cells for cell therapy, that no longer have the disease causing mutation.

Huntington's disease (HD) is a devastating, neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems. It typically becomes noticeable in mid-adult life, with symptoms beginning between 35 and 44 years of age. Life expectancy following onset of visual symptoms is about 20 years. The worldwide prevalence of HD is 5-10 cases per 100,000 persons. More than a quarter of a million Americans have HD or are "at risk" of inheriting the disease from an affected parent. Key to the disease process is the formation of specific protein aggregates (essentially abnormal clumps) inside some neurons.

All humans have two copies of the Huntingtin gene (HTT), which codes for the protein Huntingtin (Htt). Part of this gene is a repeated section called a trinucleotide repeat, which varies in length between individuals and may change between generations. When the length of this repeated section reaches a certain threshold, it produces an altered form of the protein, called mutant Huntingtin protein (mHtt). Scientists in the Ellerby lab corrected the mutation by replacing the expanded trinucleotide repeat with a normal repeat using homologous recombination. Homologous recombination is a type of genetic recombination where two molecules of DNA are exchanged. In this case the diseased DNA sequence is exchanged for the normal DNA sequence.

Contributors to the work: Mahru An and Ningzhe Zhang are shared first authors of this study. Other Buck Institute researchers involved in the study include Gary Scott, Daniel Montoro, Tobias Wittkop, and faculty members Sean Mooney and Simon Melov. The work was funded by the Buck Institute and the National Institutes of Health.

About the Buck Institute for Research on Aging The Buck Institute is the U.S.s first and foremost independent research organization devoted to Geroscience focused on the connection between normal aging and chronic disease. Based in Novato, CA, The Buck is dedicated to extending Healthspan, the healthy years of human life and does so utilizing a unique interdisciplinary approach involving laboratories studying the mechanisms of aging and those focused on specific diseases. Buck scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimers and Parkinsons, cancer, cardiovascular disease, macular degeneration, diabetes and stroke. In their collaborative research, they are supported by the most recent developments in genomics, proteomics and bioinformatics. For more information: http://www.thebuck.org.

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Scientists Correct Huntington's Mutation in Induced Pluripotent Stem Cells

Main Category: Huntingtons Disease Also Included In: Stem Cell Research Article Date: 28 Jun 2012 - 9:00 PDT

Current ratings for: Huntington's Research Tool Developed Using Stem Cells

Cedars-Sinai scientists have joined with expert colleagues around the globe in using stem cells to develop a laboratory model for Huntington's disease, allowing researchers for the first time to test directly on human cells potential treatments for this fatal, inherited disorder.

As explained in a paper published June 28 on the Cell Stem Cell website and scheduled for print in the journal's Aug. 3 issue, scientists at Cedars-Sinai's Regenerative Medicine Institute and the University of Wisconsin took skin cells from patients with Huntington's disease and reprogrammed them into powerful stem cells; these were then made into the nervous system cells affected by the disease. Seven laboratories around the world collaborated to demonstrate the cells had hallmarks of Huntington's.

"This Huntington's 'disease in a dish' will enable us for the first time to test therapies on human Huntington's disease neurons," said Clive Svendsen, PhD, director of the Cedars-Sinai Regenerative Medicine Institute and a senior author of the study. "In addition to increasing our understanding of this disorder and offering a new pathway to identifying treatments, this study is remarkable because of the extensive interactions between a large group of scientists focused on developing this model. It's a new way of doing trailblazing science."

The Huntington's Disease iPSC Consortium united some of the world's top scientists working on this disease. Cedars-Sinai researchers took skin cells from a several Huntington's patients, including a six-year-old with a severe juvenile form of the disease. They genetically reprogrammed these tissues into induced pluripotent stem cells, which can be made into any type of cell in the body. The cells lines were banked by scientists at Cedars-Sinai and scrutinized by all consortium members for differences that may have led to the disease. These cell lines are now an important resource for Huntington's researchers and have been made available via a National Institutes of Health-funded repository at Coriell Institute for Medical Research in New Jersey.

Huntington's, known to the public, for example, as the cause of folksinger Woody Guthrie's death, typically strikes patients in midlife. It causes jerky, twitching motions, loss of muscle control, psychiatric disorders and dementia; the disease ultimately is fatal. In rare, severe cases, the disorder appears in childhood.

Researchers believe that Huntington's results from a mutation in the huntintin gene, leading to production of an abnormal protein and ultimately cell death in specific areas of the brain that control movement and cognition. There is no cure for Huntington's, nor therapies to slow its progression.

The consortium showed Huntington's cell deficits or how they differ from normal cells, including that they were less likely to survive cultivation in the petri dish. Scientists tried depriving them of a growth factor present around normal cells, or "stressing" them, and found that Huntington's neurons died even faster.

"It was great that these characteristics were seen not only in our laboratory, but by all of the consortium members using different techniques," said Virginia Mattis, a post-doctoral scientist at the Cedars-Sinai Regenerative Medicine Institute and one of the lead authors of the study. "It was very reassuring and significantly strengthens the value of this study."

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Huntington's Research Tool Developed Using Stem Cells

Public release date: 28-Jun-2012 [ | E-mail | Share ]

Contact: Tom Vasich tmvasich@uci.edu 949-824-6455 University of California - Irvine

Irvine, Calif., June 28, 2012 An international consortium of Huntington's disease experts, including several from the Sue & Bill Gross Stem Cell Research Center at UC Irvine, has generated a human model of the deadly inherited disorder directly from the skin cells of affected patients.

The re-created neurons, which live in a petri dish, will help researchers better understand what disables and kills brain cells in people with HD and let them gauge the effects of potential drug therapies on cells that are otherwise locked deep in the brain.

UCI scientists were part of a consortium that in 1993 identified the autosomal dominant gene mutation responsible for HD, but there is still no cure, and no treatments are available to even slow its onset or progression. The research, published online today in the journal Cell Stem Cell, is the work of the Huntington's Disease iPSC Consortium. Participants examined several other cell lines and control cell lines to ensure that their results were consistent and reproducible in different labs.

"Our discovery will enable us for the first time to test therapies on human Huntington's disease neurons," said Leslie Thompson, UCI professor of psychiatry & human behavior and neurobiology & behavior, one of the world's leading HD experts and a senior author of the study. "This has been a remarkable time in HD research, with the advent of stem cell technologies that have allowed these scientific advancements. Also, having a team of scientists working together as a consortium has benefited the research tremendously and accelerated its pace."

Leslie Lock, a UCI assistant professor of developmental & cell biology and biological chemistry whose lab helped develop the induced pluripotent stem cells (iPSC), added: "It's exciting to be carrying out work that provides hope for HD patients and their families."

Thompson said that UCI scientists will use the new model to study the specific gene expression changes in human brain cells that trigger the onset of HD, helping them understand how these changes happen and how to correct them.

Huntington's disease afflicts about 30,000 people in the U.S. typically striking in midlife and another 75,000 carry the gene that will eventually lead to it. Caused by a mutation in the gene for a protein called huntingtin, the disease damages brain cells so that individuals with HD progressively lose their ability to walk, talk and reason. It invariably culminates in death. While rare, HD is the most common inherited neurodegenerative disease.

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Human model of Huntington's disease created from skin's stem cells

Newswise LOS ANGELES (EMBARGOED UNTIL NOON EDT ON JUNE 28, 2012) Cedars-Sinai scientists have joined with expert colleagues around the globe in using stem cells to develop a laboratory model for Huntingtons disease, allowing researchers for the first time to test directly on human cells potential treatments for this fatal, inherited disorder.

As explained in a paper published June 28 on the Cell Stem Cell website and scheduled for print in the journals Aug. 3 issue, scientists at Cedars-Sinais Regenerative Medicine Institute and the University of Wisconsin took skin cells from patients with Huntingtons disease and reprogrammed them into powerful stem cells; these were then made into the nervous system cells affected by the disease. Seven laboratories around the world collaborated to demonstrate the cells had hallmarks of Huntingtons.

This Huntingtons disease in a dish will enable us for the first time to test therapies on human Huntingtons disease neurons, said Clive Svendsen, PhD, director of the Cedars-Sinai Regenerative Medicine Institute and a senior author of the study. In addition to increasing our understanding of this disorder and offering a new pathway to identifying treatments, this study is remarkable because of the extensive interactions between a large group of scientists focused on developing this model. Its a new way of doing trailblazing science.

The Huntingtons Disease iPSC Consortium united some of the worlds top scientists working on this disease. Cedars-Sinai researchers took skin cells from a several Huntingtons patients, including a six-year-old with a severe juvenile form of the disease. They genetically reprogrammed these tissues into induced pluripotent stem cells, which can be made into any type of cell in the body. The cells lines were banked by scientists at Cedars-Sinai and scrutinized by all consortium members for differences that may have led to the disease. These cell lines are now an important resource for Huntingtons researchers and have been made available via a National Institutes of Health-funded repository at Coriell Institute for Medical Research in New Jersey.

Huntingtons, known to the public, for example, as the cause of folksinger Woody Guthries death, typically strikes patients in midlife. It causes jerky, twitching motions, loss of muscle control, psychiatric disorders and dementia; the disease ultimately is fatal. In rare, severe cases, the disorder appears in childhood.

Researchers believe that Huntingtons results from a mutation in the huntintin gene, leading to production of an abnormal protein and ultimately cell death in specific areas of the brain that control movement and cognition. There is no cure for Huntingtons, nor therapies to slow its progression.

The consortium showed Huntingtons cell deficits or how they differ from normal cells, including that they were less likely to survive cultivation in the petri dish. Scientists tried depriving them of a growth factor present around normal cells, or stressing them, and found that Huntingtons neurons died even faster.

It was great that these characteristics were seen not only in our laboratory, but by all of the consortium members using different techniques, said Virginia Mattis, a post-doctoral scientist at the Cedars-Sinai Regenerative Medicine Institute and one of the lead authors of the study. It was very reassuring and significantly strengthens the value of this study.

This new model will provide the foundation for a new round of experiments by the consortium funded by a new grant from the NIH and the California Institute for Regenerative Medicine.

The Cedars-Sinais Regenerative Medicine Institute has made a major commitment to projects like this Huntingtons study in which stem cell research helps to advance understanding of human disease and open new and innovative methods to identify treatments and cures. The institute has developed an induced pluripotent stem cell core facility and recruited faculty to work in this emerging area of regenerative medicine research.

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Cedars-Sinai Researchers, with Stem Cells and Global Colleagues, Develop Huntington's Research Tool