By Traci Pedersen Associate News Editor Reviewed by John M. Grohol, Psy.D. on May 25, 2014

Neurons generated from the skin cells of schizophrenia patients behave strangely in the early developmental stages, offering clues that might lead to earlier detection and treatment, according to scientists from the Salk Institute.

The study, published in the journal Molecular Psychiatry, supports the theory that the neurological dysfunction that eventually leads to schizophrenia may begin in the brains of fetuses.

This study aims to investigate the earliest detectable changes in the brain that lead to schizophrenia, said Fred H. Gage, Ph.D., professor of genetics at Salk. We were surprised at how early in the developmental process that defects in neural function could be detected.

Up until now, scientists could only study the disease by examining the brains of cadavers; but age, stress, medication, or drug abuse had often changed or damaged these brains, making it harder to figure out the where it all began.

The Salk scientists were able to go around this obstacle by using stem cell technologies. They took skin cells from patients, coaxed the cells back to an earlier stem cell form and then prompted them to grow into very early-stage neurons called neural progenitor cells (NPCs). These NPCs are similar to cells found in the brain of a fetus.

The researchers tested the cells in two ways: In one test, they looked at how far the cells moved and interacted with particular surfaces; in the other test, they looked at cell stress by imaging mitochondria, tiny organelles that generate energy for the cells.

On both tests, the NPCs from schizophrenia patients differed in significant ways from those taken from people without the disease.

In particular, cells taken from people with schizophrenia showed unusual activity in two major classes of proteins: those involved in adhesion and connectivity, and those involved in oxidative stress. Schizophrenia neural cells seemed to have aberrant migration (which may result in the poor connectivity seen later in the brain) and greater levels of oxidative stress.

These results support the current theory that eventsduring pregnancy can contribute to schizophrenia, even though symptoms typically dont begin until early adulthood. For example, previous research suggests that pregnant mothers who experience infection, malnutrition, or extreme stress are at greater risk of having children with schizophrenia.

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Skin Cell Research Suggests Schizophrenia Begins in Womb

New Delhi, May 24 (IANS) It's that time of the year again when the sun shines the brightest only to take your skin's shine away! How about trying some different ways to get flawless skin?

Sangeeta Amladi, head medical services with Kaya Skin Clinic, shares tips that will help one look radiant during summer.

* Say goodbye to pigmentation and uneven skin tone with skin lightening miracles. This skincare treatment is designed to reduce tan and visibly lighten your skin, leaving it fresh and glowing.

* Sun is known to cause skin damage, including wrinkles and aging skin disorders. Some beauty brands are hence using a new miracle ingredient stem cell in anti-aging creams. Stem cells have a remarkable potential to not only repair the body internally and rejuvenate the skin cells but it also slow skin aging. This new technology is a breakthrough solution to flaunt an ageless beautiful skin.

* With the increased level of pollution, there is a growing need for detoxifying the skin. Detox mask contains active blend of antioxidants which exfoliates and deep clean the pores without over-drying the skin. This gentle treatment helps detoxify, hydrate, and rejuvenate skin thus giving it a natural glow.

* Dare to go backless this summer with 'Back' beauty! Pamper your back with a microdermabrasion therapy (a light cosmetic procedure) to sport that spotless and smooth back. This therapy cleanses, polishes and moisturizes the highly ignored skin on our back. It removes the layer of dead skin to reveal a radiant and attractive back

* With the sun soaking all the moisture from your skin, only drinking water is not sufficient to keep it moisturized. Moisturizer with ceramides is another new age product that helps maintain the skin's lipid balance. There are also some studies that have shown that these ceramide induced moisturizers treat eczema as well. A ceremide induced moisturizer is definitely an answer to pamper dry skin

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Cosmetic essentials for flawless you

15 hours ago These are mature nerve cells generated from human cells using enhanced transcription factors. Credit: Fahad Ali

A new method of generating mature nerve cells from skin cells could greatly enhance understanding of neurodegenerative diseases, and could accelerate the development of new drugs and stem cell-based regenerative medicine.

The nerve cells generated by this new method show the same functional characteristics as the mature cells found in the body, making them much better models for the study of age-related diseases such as Parkinson's and Alzheimer's, and for the testing of new drugs.

Eventually, the technique could also be used to generate mature nerve cells for transplantation into patients with a range of neurodegenerative diseases.

By studying how nerves form in developing tadpoles, researchers from the University of Cambridge were able to identify ways to speed up the cellular processes by which human nerve cells mature. The findings are reported in the May 27th edition of the journal Development.

Stem cells are our master cells, which can develop into almost any cell type within the body. Within a stem cell, there are mechanisms that tell it when to divide, and when to stop dividing and transform into another cell type, a process known as cell differentiation. Several years ago, researchers determined that a group of proteins known as transcription factors, which are found in many tissues throughout the body, regulate both mechanisms.

More recently, it was found that by adding these proteins to skin cells, they can be reprogrammed to form other cell types, including nerve cells. These cells are known as induced neurons, or iN cells. However, this method generates a low number of cells, and those that are produced are not fully functional, which is a requirement in order to be useful models of disease: for example, cortical neurons for stroke, or motor neurons for motor neuron disease.

In addition, for age-related diseases such as Parkinson's and Alzheimer's, both of which affect millions worldwide, mature nerve cells which show the same characteristics as those found in the body are crucial in order to enhance understanding of the disease and ultimately determine the best way to treat it.

"When you reprogramme cells, you're essentially converting them from one form to another but often the cells you end up with look like they come from embryos rather than looking and acting like more mature adult cells," said Dr Anna Philpott of the Department of Oncology, who led the research. "In order to increase our understanding of diseases like Alzheimer's, we need to be able to work with cells that look and behave like those you would see in older individuals who have developed the disease, so producing more 'adult' cells after reprogramming is really important."

By manipulating the signals which transcription factors send to the cells, Dr Philpott and her collaborators were able to promote cell differentiation and maturation, even in the presence of conflicting signals that were directing the cell to continue dividing.

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Functional nerve cells from skin cells

St. Petersburg, FL (PRWEB) May 20, 2014

A breakthrough for rejuvenating aging skin today includes topical stem cells rich in Growth Factors. These are non-embryonic stem cells.

Collagen is lost during the aging process as production slows down, a contributing factor in the formation of wrinkles, lines, sagging and thinning of skin.

"A very effective way to reduce wrinkles, improve skin quality and boost collagen levels is through Human Fibroblast Conditioned Media," says Kathy Heshelow, founder of Sublime Beauty. "Human Fibroblast Conditioned Media contains key ingredients for rejuvenation of skinespecially natural Growth Factors and other proteins."

2 reasons why these Growth Factors are key for anti-aging skin care:

1) Growth Factors, when used topically, stimulate skin to create more collagen. Results include smoother, healthier skin with diminished wrinkles. Collagen is the structure holding up skin, essential for smoothness.

2) Growth Factors help to replace and regenerate the nutrients needed by skin for rejuvenation. It promotes skin tissue repair and strengthens the elastic fibers which give the skin its softness and suppleness.

"We added our stem cell serum to the Sublime Beauty line for those that wanted a higher end, scientific formula," says Heshelow. "Our serum is of high purity with no fillers and is made in the U.S under strict conditions."

Expensive to make, Heshelow says the Sublime Beauty serum is less expensive than many similar serums found on the market, which can range from $300 to $500. "Our serum retails under $160," Heshelow says.

Use twice daily and see first results in about 2 weeks.

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2 Reasons Why Growth Factors and Stem Cells are a Breakthough for Aging Skin, Says Sublime Beauty

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Newswise SALT LAKE CITY In the body, a skin cell will always be skin, and a heart cell will always be heart. But in the first hours of life, cells in the nascent embryo become totipotent: they have the incredible flexibility to mature into skin, heart, gut, or any type of cell.

It was long assumed that the joining of egg and sperm launched a dramatic change in how and which genes were expressed. Instead, new research shows that totipotency is a step-wise process, manifesting as early as in precursors to sperm, called adult germline stem cells (AGSCs), which reside in the testes.

The study was co-led by Bradley Cairns, Ph.D., University of Utah professor of oncological sciences, and Huntsman Cancer Institute investigator, and Ernesto Guccione, Ph.D., of the Agency for Science Technology and Research in Singapore. They worked closely with first author and Huntsman Cancer Institute postdoctoral fellow, Saher Sue Hammond, Ph.D. The research was published online in the journal Cell Stem Cell.

Typically, sperm precursors live a mundane life. They divide, making more cells like themselves, until they receive the signal instructing them to mature into sperm.

There is evidence, however, that these cells have the potential to do more. Under the unusual conditions that promote the cells to form dense cancerous masses called testicular teratomas, the young sperm transform into precursors of skin, muscle, and gut.

This realization prompted the investigators to examine the gene program within sperm precursors. They wondered, would it be like that of a cell that is destined to become a single cell type, or like that of a cell with the potential to become anything?

The answer, they found, is that the sperm precursors are somewhere in between. The most telling evidence is the status of a quartet of genes: Lefty, Sox2, Nanog, and Prdm14. When activated, the genes can trigger a cascade of events that give cells stem cell properties. In cells limited to becoming one cell type, the genes are silent.

Yet in sperm precursors, the genes bear a code of chemical tags, called methylation groups, indicating that the four genes are silenced, but poised to become active. In other words, embedded within these cells, is the potential to become totipotent.

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The Young Sperm, Poised for Greatness

Harvard Stem Cell Institute (HSCI) scientists at Massachusetts General Hospital have a potential solution for how to more effectively kill tumor cells using cancer-killing viruses. The investigators report that trapping virus-loaded stem cells in a gel and applying them to tumors significantly improved survival in mice with glioblastoma multiforme, the most common brain tumor in human adults and also the most difficult to treat.

The work, led by Khalid Shah, MS, PhD, an HSCI Principal Faculty member, is published in the Journal of the National Cancer Institute. Shah heads the Molecular Neurotherapy and Imaging Laboratory at Massachusetts General Hospital.

Cancer-killing or oncolytic viruses have been used in numerous phase 1 and 2 clinical trials for brain tumors but with limited success. In preclinical studies, oncolytic herpes simplex viruses seemed especially promising, as they naturally infect dividing brain cells. However, the therapy hasn't translated as well for human patients. The problem previous researchers couldn't overcome was how to keep the herpes viruses at the tumor site long enough to work.

Shah and his team turned to mesenchymal stem cells (MSCs) -- a type of stem cell that gives rise to bone marrow tissue -- which have been very attractive drug delivery vehicles because they trigger a minimal immune response and can be utilized to carry oncolytic viruses. Shah and his team loaded the herpes virus into human MSCs and injected the cells into glioblastoma tumors developed in mice. Using multiple imaging markers, it was possible to watch the virus as it passed from the stem cells to the first layer of brain tumor cells and subsequently into all of the tumor cells.

"So, how do you translate this into the clinic?" asked Shah, who also is an Associate Professor at Harvard Medical School.

"We know that 70-75 percent of glioblastoma patients undergo surgery for tumor debulking, and we have previously shown that MSCs encapsulated in biocompatible gels can be used as therapeutic agents in a mouse model that mimics this debulking," he continued. "So, we loaded MSCs with oncolytic herpes virus and encapsulated these cells in biocompatible gels and applied the gels directly onto the adjacent tissue after debulking. We then compared the efficacy of virus-loaded, encapsulated MSCs versus direct injection of the virus into the cavity of the debulked tumors."

Using imaging proteins to watch in real time how the virus combated the cancer, Shah's team noticed that the gel kept the stem cells alive longer, which allowed the virus to replicate and kill any residual cancer cells that were not cut out during the debulking surgery. This translated into a higher survival rate for mice that received the gel-encapsulated stem cells.

"They survived because the virus doesn't get washed out by the cerebrospinal fluid that fills the cavity," Shah said. "Previous studies that have injected the virus directly into the resection cavity did not follow the fate of the virus in the cavity. However, our imaging and side-by-side comparison studies showed that the naked virus rarely infects the residual tumor cells. This could give us insight into why the results from clinical trials with oncolytic viruses alone were modest."

The study also addressed another weakness of cancer-killing viruses, which is that not all brain tumors are susceptible to the therapy. The researchers' solution was to engineer oncolytic herpes viruses to express an additional tumor-killing agent, called TRAIL. Again, using mouse models of glioblastoma -- this time created from brain tumor cells that were resistant to the herpes virus -- the therapy led to increased animal survival.

"Our approach can overcome problems associated with current clinical procedures," Shah said. "The work will have direct implications for designing clinical trials using oncolytic viruses, not only for brain tumors, but for other solid tumors."

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Herpes-loaded stem cells used to kill brain tumors

Concerns that stem cells could cause cancer in recipients are fading further with a new study

New bone formation (stained bright green under ultra-violet light) was seen in monkeys given their own reprogrammed stem cells. Courtesy of Nature magazine

A major concern over using stem cells is the risk of tumors: but now a new study shows that It takes a lot of effort to get induced pluripotent stem (iPS) cells to grow into tumors after they have been transplanted into a monkey. The findings will bolster the prospects of one day using such cells clinically in humans.

Making iPS cells from an animal's own skin cells and then transplanting them back into the creature also does not trigger an inflammatory response as long as the cells have first been coaxed to differentiate towards a more specialized cell type. Both observations, published inCell Reports today, bode well for potential cell therapies.

It's important because the field is very controversial right now, saysAshleigh Boyd,a stem-cell researcher at University College London, who was not involved in the work. It is showing that the weight of evidence is pointing towards the fact that the cells won't be rejected.

Pluripotent stem cells can be differentiated into many different specialized cell types in culture and so are touted for their potential as therapies to replace tissue lost in diseases such as Parkinsons and some forms of diabetes and blindness. iPS cells, which are made by reprogramming adult cells, have an extra advantage because transplants made from them could be genetically matched to the recipient.

Researchers all over the world are pursuing therapies based on iPS cells, and a group in Japan began enrolling patients for a human study last year. But work in mice has suggested controversially that even genetically matched iPS cellscan trigger an immune response, and pluripotent stem cells can also form slow-growing tumors, another safety concern.

Closer to human Cynthia Dunbar, a stem-cell biologist at the National Institutes of Health in Bethesda, Maryland, who led the new study, decided to evaluate both concerns in healthy rhesus macaques. Human stem cells are normally only studied for their ability to form tumors in mice as a test of pluripotency if the animals immune systems are compromised, she says.

We really wanted to set up a model that was closer to human. It was somewhat reassuring that in a normal monkey with a normal immune system you had to give a whole lot of immature cells to get any kind of tumour to grow, and they were very slow growing.

Dunbar and her team made iPS cells from skin and white blood cells from two rhesus macaques, and transplanted the iPS cells back into the monkeys that provided them. It took 20 times as many iPS cells to form a tumor in a monkey, compared with the numbers needed in an immunocompromised mouse. Such information will be valuable for assessing safety risks of potential therapies, Dunbar says. And although the iPS cells did trigger a mild immune response attracting white blood cells and causing local inflammation iPS cells that had first been differentiated to a more mature state did not.

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New Stem Cell Finding Bodes Well for Future Medical Use in Humans

A number of ingredients like ceramides, collagen, stem cells and antioxidants that are commonly associated with cosmetics are being featured in products for the hair. Do they work as well?

In the quest for a healthy and shining mane, a number of new products are being launched in the market on a regular basis. It has been observed that many of these are said to contain elements that are normally associated with skin care. Products with collagen, ceramides, hyaluronic acid, stem cells and so on have long been proven beneficial to plump up skin, reduce fine lines, lighten dark spots and keep skin healthy and radiant. However, recently a number of these have been seen in hair care products like shampoos and conditioners. The question remains though is of they work just as well on the mane. Copper peptides, for example is considered an effective skin regeneration ingredient and research shows it works well for the scalp too producing thicker, healthier hair. Ceramides can be effective in forming a protective coat around the hair shaft and strengthening it, while collagen helps hair hold onto moisture making it look thicker and fuller. Antioxidants are said to neutralise the free radicals preventing dullness of locks.

SCALP IS SIMILAR TO SKIN Tisha Kapur Khurana, beauty expert and executive director, Bottega di Lungavita explains similar ingredients can be used on the skin and hair sometimes because the scalp is covered with thicker skin similar to the rest of our body. It is a thick layer of skin with many sebaceous glands which produce oil or sebum to protect the hair. Collagen is a protein that is found in the body and is a necessity for good health. The collagen supplements let hair grow long and strong. It increases the body's natural hair-building proteins. Moreover, if applied to the scalp, it can reduce the look and dryness of grey hair. Even stem cells work as the hair follicles contain cells which may lead to successfully treating baldness. When buying a product you should always consider the hair type curly or straight as well as thick or fine and accordingly choose products, she says.

BE CAREFUL It is advisable not to use similar products for your hair and skin. Your skin is very tender and it needs really mild products to cleanse and clear the dirt and impurities. On the other hand, while you do need mild products for your hair as well, the shampoos and conditioners are mild but effective enough to cleanse the grime, dandruff and other impurities that get lodged in your scalp, explains Priti Mehta, founder and director, Omved. She adds, Standard cosmetics often include synthetic and sometimes even animal-derived ingredients. When you use natural options for your skin and hair, it is likely to help your skin feel and breathe better. Anything that has SLS, parabens, preservatives, fragrance, and colours to name a few listed on it should be avoided.

HAVE SOME BENEFITS Dr Apratim Goel, dermatologist, Cutis Skin Studio says some of these ingredients can work. Collagen or ceramides are larger molecules which are doubtful on skin as well. However these ingredients have been used regularly in hair care products. However, there is no controlled studies of efficacy of these ingredients in hair. Stem cells and antioxidants, though, do work for hair. Stem cell injections are a regular treatment for boosting hair growth. Further, plant stem cells are available as hair serums and give good results against hair loss. Regarding antioxidants, they are very important for hair care as hair especially coloured or treated locks are very prone to damage from sun as well as chemical exposure.

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Do products used in cosmetics work for the hair?

Harvard scientists have merged stem cell and organ-on-a-chip technologies to grow, for the first time, functioning human heart tissue carrying an inherited cardiovascular disease. The research appears to be a big step forward for personalized medicine because it is working proof that a chunk of tissue containing a patient's specific genetic disorder can be replicated in the laboratory.

The work, published in May 2014 in Nature Medicine, is the result of a collaborative effort bringing together scientists from the Harvard Stem Cell Institute, the Wyss Institute for Biologically Inspired Engineering, Boston Children's Hospital, the Harvard School of Engineering and Applied Sciences, and Harvard Medical School. It combines the organs-on-chips expertise of Kevin Kit Parker, PhD, and stem cell and clinical insights by William Pu, MD.

A release from Harvard explains that using their interdisciplinary approach, the investigators modeled the cardiovascular disease Barth syndrome, a rare X-linked cardiac disorder caused by mutation of a single gene called Tafazzin, or TAZ. The disorder, which is currently untreatable, primarily appears in boys, and is associated with a number of symptoms affecting heart and skeletal muscle function.

The researchers took skin cells from two Barth syndrome patients, and manipulated the cells to become stem cells that carried these patients' TAZ mutations. Instead of using the stem cells to generate single heart cells in a dish, the cells were grown on chips lined with human extracellular matrix proteins that mimic their natural environment, tricking the cells into joining together as they would if they were forming a diseased human heart. The engineered diseased tissue contracted very weakly, as would the heart muscle seen in Barth syndrome patients. The investigators then used genome editinga technique pioneered by Harvard collaborator George Church, PhDto mutate TAZ in normal cells, confirming that this mutation is sufficient to cause weak contraction in the engineered tissue. On the other hand, delivering the TAZ gene product to diseased tissue in the laboratory corrected the contractile defect, creating the first tissue-based model of correction of a genetic heart disease. The release quotes Parker as saying, "You don't really understand the meaning of a single cell's genetic mutation until you build a huge chunk of organ and see how it functions or doesn't function. In the case of the cells grown out of patients with Barth syndrome, we saw much weaker contractions and irregular tissue assembly. Being able to model the disease from a single cell all the way up to heart tissue, I think that's a big advance."

Furthermore, the scientists discovered that the TAZ mutation works in such a way to disrupt the normal activity of mitochondria, often called the power plants of the cell for their role in making energy. However, the mutation didn't seem to affect overall energy supply of the cells. In what could be a newly identified function for mitochondria, the researchers describe a direct link between mitochondrial function and a heart cell's ability to build itself in a way that allows it to contract. "The TAZ mutation makes Barth syndrome cells produce an excess amount of reactive oxygen species or ROSa normal byproduct of cellular metabolism released by mitochondriawhich had not been recognized as an important part of this disease," said Pu, who cares for patients with the disorder. "We showed that, at least in the laboratory, if you quench the excessive ROS production then you can restore contractile function," Pu added. "Now, whether that can be achieved in an animal model or a patient is a different story, but if that could be done, it would suggest a new therapeutic angle." His team is now trying to translate this finding by doing ROS therapy and gene replacement therapy in animal models of Barth syndrome to see if anything could potentially help human patients. At the same time, the scientists are using their human 'heart disease-on-a-chip' as a testing platform for drugs that are potentially under trial or already approved that might be useful to treat the disorder.

"We tried to thread multiple needles at once and it certainly paid off," Parker said. "I feel that the technology that we've got arms industry and university-based researchers with the tools they need to go after this disease." Both Parker and Pu, who first talked about collaborating at a 2012 Stockholm conference, credit their partnership and scientific consilience for the success of this research. Parker asserted that the 'organs-on-chips' technology that has been a flagship of his lab only worked so fast and well because of the high quality of Pu's patient-derived cardiac cells. "When we first got those cells down on the chip, Megan, one of the joint first authors, texted me 'this is working,'" he recalled. "We thought we'd have a much harder fight." "When I'm asked what's unique about being at Harvard, I always bring up this story," Pu said. "The diverse set of people and cutting-edge technology available at Harvard certainly made this study possible." The researchers also involved in this work include: Joint first authors Gang Wang, MD, of Boston Children's Hospital, and Megan McCain, PhD, who earned her degree at the Harvard School of Engineering and Applied Sciences and is now an assistant professor at the University of Southern California. Amy Roberts, MD, of Boston Children's Hospital, and Richard Kelley, MD, PhD, at the Kennedy Krieger Institute provided patient data and samples, and Frdric Vaz, PhD, and his team at the Academic Medical Center in the Netherlands conducted additional analyses. Technical protocols were shared by Kenneth Chien, MD, PhD, at the Karolinska Institutet.

Kevin Kit Parker, PhD, is the Tarr Family Professor of Bioengineering and Applied Physics in Harvard's School of Engineering and Applied Sciences, a Core Faculty member of the Wyss Institute for Biologically Inspired Engineering, and a Principal Faculty member of the Harvard Stem Cell Institute. William Pu, MD, is an Associate Professor at Harvard Medical School, a member of the Department of Cardiology at Boston Children's Hospital, and an Affiliated Faculty member of the Harvard Stem Cell Institute. George Church, PhD, is a Professor of Genetics at Harvard Medical School and a Core Faculty member of the Wyss Institute of Biologically Inspired Engineering. The work was supported by the Barth Syndrome Foundation, Boston Children's Hospital, the National Institutes of Health, and charitable donations from Edward Marram, Karen Carpenter, and Gail Federici Smith.

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Stem Cells Make Heart Disease-on-a-Chip

Using new stem cell technology, scientists at the Salk Institute have shown that neurons generated from the skin cells of people with schizophrenia behave strangely in early developmental stages, providing a hint as to ways to detect and potentially treat the disease early.

The findings of the study, published online in April's Molecular Psychiatry, support the theory that the neurological dysfunction that eventually causes schizophrenia may begin in the brains of babies still in the womb.

"This study aims to investigate the earliest detectable changes in the brain that lead to schizophrenia," says Fred H. Gage, Salk professor of genetics. "We were surprised at how early in the developmental process that defects in neural function could be detected."

Currently, over 1.1 percent of the world's population has schizophrenia, with an estimated three million cases in the United States alone. The economic cost is high: in 2002, Americans spent nearly $63 billion on treatment and managing disability. The emotional cost is higher still: 10 percent of those with schizophrenia are driven to commit suicide by the burden of coping with the disease.

Although schizophrenia is a devastating disease, scientists still know very little about its underlying causes, and it is still unknown which cells in the brain are affected and how. Previously, scientists had only been able to study schizophrenia by examining the brains of patients after death, but age, stress, medication or drug abuse had often altered or damaged the brains of these patients, making it difficult to pinpoint the disease's origins.

The Salk scientists were able to avoid this hurdle by using stem cell technologies. They took skin cells from patients, coaxed the cells to revert back to an earlier stem cell form and then prompted them to grow into very early-stage neurons (dubbed neural progenitor cells or NPCs). These NPCs are similar to the cells in the brain of a developing fetus.

The researchers generated NPCs from the skin cells of four patients with schizophrenia and six people without the disease. They tested the cells in two types of assays: in one test, they looked at how far the cells moved and interacted with particular surfaces; in the other test, they looked at stress in the cells by imaging mitochondria, which are tiny organelles that generate energy for the cells.

On both tests, the Salk team found that NPCs from people with schizophrenia differed in significant ways from those taken from unaffected people.

In particular, cells predisposed to schizophrenia showed unusual activity in two major classes of proteins: those involved in adhesion and connectivity, and those involved in oxidative stress. Neural cells from patients with schizophrenia tended to have aberrant migration (which may result in the poor connectivity seen later in the brain) and increased levels of oxidative stress (which can lead to cell death).

These findings are consistent with a prevailing theory that events occurring during pregnancy can contribute to schizophrenia, even though the disease doesn't manifest until early adulthood. Past studies suggest that mothers who experience infection, malnutrition or extreme stress during pregnancy are at a higher risk of having children with schizophrenia. The reason for this is unknown, but both genetic and environmental factors likely play a role.

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Stem cell technology points to early indicators of schizophrenia

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Newswise LA JOLLAUsing new stem cell technology, scientists at the Salk Institute have shown that neurons generated from the skin cells of people with schizophrenia behave strangely in early developmental stages, providing a hint as to ways to detect and potentially treat the disease early.

The findings of the study, published online in April's Molecular Psychiatry, support the theory that the neurological dysfunction that eventually causes schizophrenia may begin in the brains of babies still in the womb.

"This study aims to investigate the earliest detectable changes in the brain that lead to schizophrenia," says Fred H. Gage, Salk professor of genetics. "We were surprised at how early in the developmental process that defects in neural function could be detected."

Currently, over 1.1 percent of the world's population has schizophrenia, with an estimated three million cases in the United States alone. The economic cost is high: in 2002, Americans spent nearly $63 billion on treatment and managing disability. The emotional cost is higher still: 10 percent of those with schizophrenia are driven to commit suicide by the burden of coping with the disease.

Although schizophrenia is a devastating disease, scientists still know very little about its underlying causes, and it is still unknown which cells in the brain are affected and how. Previously, scientists had only been able to study schizophrenia by examining the brains of patients after death, but age, stress, medication or drug abuse had often altered or damaged the brains of these patients, making it difficult to pinpoint the disease's origins.

The Salk scientists were able to avoid this hurdle by using stem cell technologies. They took skin cells from patients, coaxed the cells to revert back to an earlier stem cell form and then prompted them to grow into very early-stage neurons (dubbed neural progenitor cells or NPCs). These NPCs are similar to the cells in the brain of a developing fetus.

The researchers generated NPCs from the skin cells of four patients with schizophrenia and six people without the disease. They tested the cells in two types of assays: in one test, they looked at how far the cells moved and interacted with particular surfaces; in the other test, they looked at stress in the cells by imaging mitochondria, which are tiny organelles that generate energy for the cells.

On both tests, the Salk team found that NPCs from people with schizophrenia differed in significant ways from those taken from unaffected people.

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New Stem Cell Research Points to Early Indicators of Schizophrenia

Image Caption: Researchers use modified RNA transfection to correct genetic dysfunction in heart stem cells derived from Barth syndrome patients. The series of images show how inserting modified RNA into diseased cells causes the cells to produce functioning versions of the TAZ protein (first image: in green) that correctly localize in the mitochondria (second image: in red). When the images are merged to demonstrate this localization, green overlaps with red, giving the third image a yellow color. Credit: Gang Wang and William Pu/Boston Children's Hospital

[ Watch The Video: Cardiac Tissue Contractile Strength Differences Shown Using Heart-On-A-Chip ]

Harvard University

Harvard scientists have merged stem cell and organ-on-a-chip technologies to grow, for the first time, functioning human heart tissue carrying an inherited cardiovascular disease. The research appears to be a big step forward for personalized medicine, as it is working proof that a chunk of tissue containing a patients specific genetic disorder can be replicated in the laboratory.

The work, published in Nature Medicine, is the result of a collaborative effort bringing together scientists from the Harvard Stem Cell Institute, the Wyss Institute for Biologically Inspired Engineering, Boston Childrens Hospital, the Harvard School of Engineering and Applied Sciences, and Harvard Medical School. It combines the organs-on-chips expertise of Kevin Kit Parker, PhD, and stem cell and clinical insights by William Pu, MD.

Using their interdisciplinary approach, the investigators modeled the cardiovascular disease Barth syndrome, a rare X-linked cardiac disorder caused by mutation of a single gene called Tafazzin, or TAZ. The disorder, which is currently untreatable, primarily appears in boys, and is associated with a number of symptoms affecting heart and skeletal muscle function.

The researchers took skin cells from two Barth syndrome patients, and manipulated the cells to become stem cells that carried these patients TAZ mutations. Instead of using the stem cells to generate single heart cells in a dish, the cells were grown on chips lined with human extracellular matrix proteins that mimic their natural environment, tricking the cells into joining together as they would if they were forming a diseased human heart. The engineered diseased tissue contracted very weakly, as would the heart muscle seen in Barth syndrome patients.

The investigators then used genome editinga technique pioneered by Harvard collaborator George Church, PhDto mutate TAZ in normal cells, confirming that this mutation is sufficient to cause weak contraction in the engineered tissue. On the other hand, delivering the TAZ gene product to diseased tissue in the laboratory corrected the contractile defect, creating the first tissue-based model of correction of a genetic heart disease.

You dont really understand the meaning of a single cells genetic mutation until you build a huge chunk of organ and see how it functions or doesnt function, said Parker, who has spent over a decade working on organs-on-chips technology. In the case of the cells grown out of patients with Barth syndrome, we saw much weaker contractions and irregular tissue assembly. Being able to model the disease from a single cell all the way up to heart tissue, I think thats a big advance.

Furthermore, the scientists discovered that the TAZ mutation works in such a way to disrupt the normal activity of mitochondria, often called the power plants of the cell for their role in making energy. However, the mutation didnt seem to affect overall energy supply of the cells. In what could be a newly identified function for mitochondria, the researchers describe a direct link between mitochondrial function and a heart cells ability to build itself in a way that allows it to contract.

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'Heart Disease-On-A-Chip' Made From Patient Stem Cells

Eczema is one of the most common skin conditions, affecting up to 30% of people in the US. Symptoms include dry, itchy skin and rashes. But according to new research, having eczema may not be all that bad; it could reduce the risk of skin cancer.

In a study published in the journal eLife, researchers from Kings College London in the UK say that eczema, also known as atopic dermatitis, activates an immune response that sheds potentially cancerous cells from the skin, preventing tumor formation.

According to the research team, including Prof. Fiona Watt of the Centre for Stem Cells and Regenerative Medicine at Kings College, previous studies have suggested that eczema may reduce the risk of skin cancer.

However, they note that this association has proven difficult to confirm in human studies, as medication for eczema may influence cancer risk. Furthermore, symptoms of the condition vary in severity in each individual.

Eczema reduced tumor formation in mice models

For their study, the team genetically engineered mice to have skin defects commonly found in humans with eczema.

They did this by removing structural proteins in the outer layers of their skin, causing them to have an abnormal skin barrier.

The researchers then tested two cancer-causing chemicals in the genetically engineered mice, as well as in normal mice.

They found that the number of benign tumors in defected mice was six times lower than the number found in the normal mice.

Further investigation revealed that although both the defected and normal mice had equal susceptibility to mutations caused by the chemicals, the defected mice had an exaggerated inflammatory response that resulted in potentially cancerous cells being shed from the skin.

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Eczema may reduce skin cancer risk

20 hours ago A signal from Transit-Amplifying Cells (TACs) activates stem cells in the hair follicle, researchers have found. Both types of cells appear in green (top), with TACs clustered lower down. The researchers identified the signal as Sonic Hedgehog. In experiments, such as this one (bottom), they disabled the signal, interfering with hair growth and regeneration.

(Phys.org) Stem cells switch off and on, sometimes dividing to produce progeny cells and sometimes resting. But scientists don't fully understand what causes the cells to toggle between active and quiet states.

New research in Elaine Fuchs' Laboratory of Mammalian Cell Biology and Development focused on stem cells in the hair follicle to determine what switches them on. The researchers found cells produced by the stem cells, progeny known at Transit-Amplifying Cells or TACs, emit a signal that tells quiet hair follicle stem cells to become active.

"Many types of mammalian stem cells produce TACs, which act as an intermediate between the stem cells and their final product: fully differentiated cells in blood, skin and elsewhere," says Ya-Chieh Hsu, who conducted the research while as a postdoc in the lab and will soon move to Harvard University. "In the past, TACs were seen as a population of cells that sat by passively cranking out tissues. No one expected them to play a regulatory role."

Hsu and Fuchs went a step further to identify the signal sent out by the TACs. They pinpointed a cell-division promoting protein called Sonic Hedgehog, which plays a role in the embryonic development of the brain, eyes and limbs.

Stem cells are medically valuable because they have the potential to produce a number of specialized cells suitable for specific roles. Stem cells' production of these differentiated cells is crucial to normal maintenance, growth and repair. Many tissues have two populations of stem cells: one that divides rarely, known as the quiescent stem cells, and another that is more prone to proliferate, known as primed stem cells. Regardless of their proliferation frequency, most stem cells in humans do not directly produce differentiated progeny cells; instead, they give rise to an intermediate proliferating population, the TACs.

The hair follicle, the tiny organ that produces a hair, forms a narrow cavity down into the skin. It cycles between rounds of growth, destruction and rest. When entering the growth phase, the primed stem cell population is always the first to divide and generates the TACs clustered lower down in the hair follicle. Primed stem cell proliferation sets the stage for the next round of hair growth, a process which ensures hairs are replaced as they are lost over time. Proliferating TACs produce the hair shaft, as well as all the cells surrounding the hair underneath the skin, which make up the follicle itself.

At the outset, Hsu and Fuchs suspected a role for both the TACs and for Sonic Hedgehog in hair regeneration.

"We noticed that the primed stem cell population gets activated early and makes the TACs, while the quiescent stem cell population only becomes activated once TACs are generated. This correlation prompted us to look for a signal that is made by the TACs. Sonic Hedgehog is that signal, as we went on to demonstrate," explained Fuchs.

In experiments described this week in Cell, Hsu disabled TACs' ability to produce the Sonic Hedgehog protein by knocking out the gene responsible in the hair follicles of adult mice. As a result, the proliferation of hair follicle stem cells and their TACs are both compromised. They further showed that it is the quiescent stem cell population which requires Sonic Hedgehog directly for proliferation.

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Stem cell progeny tell their parents when to turn on

Its much easier to defend the use of animal testing for medical research than for cosmetics testing. Yet many cosmetics companies continue to test on animals to ensure that their products dont produce negative outcomes for their human customers.

Even as medical researchers produce organs on a chip to help with drug testing, developing human skin for cosmetics testing has remained elusive. Simply cultivating skin cells in a petri dish doesnt work because the cells dont proliferate enough to be useful for many tests. And fabricating skin cells from stem cells has also fallen short, because the epidermal cells grown in a lab culture dont produce the same barrier that human skin uses to keep moisture in and toxins out.

Researchers at Kings College London and the San Francisco Veteran Affairs Medical Center report they have cleared those hurdles.

Our new method can be used to grow much greater quantities of lab-grown human epidermal equivalents, and thus could be scaled up for commercial testing of drugs and cosmetics, said Theodora Mauro, who led the San Francisco team.

Using both human embryonic stem cells and induced pluripotent stem cells, they developed keratinocytes, the cells that make up the skins protective barrier. They positioned the cells into layers while gradually reducing the humidity in the cell culture, and ended up with a stratified epidermis with skin barrier properties similar to those of normal skin. (Essentially, different proteins dominated in each layer.)

The method could viably produce enough skin samples to be used commercially for drug and cosmetics testing, according to the researchers.

An added benefit: Making the skin from stem cells means that particular diseases could be intentionally produced for study, including common skin ailments like dermatitis in which a defective skin barrier means that toxins cannot be handily repelled and become irritants. Admittedly, these diseases are neither life-threatening nor medically exciting, but they are a big nuisance for those who suffer from them. Some, like atopic dermatitis, remain poorly understood.

The ability to obtain an unlimited number of genetically identical units can be used to study a range of conditions where the skins barrier is defective due to mutations in genes involved in skin barrier formation. We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery, Mauro said.

Use of stem cell-based proxies for specific human organs, both to study disease behavior and to test drugs, is a rapidly growing market. In many cases its benefits are so hypothetical eliminating negative outcomes that would, statistically, have happened if in vitro organ tissue hadnt been used that they go unheralded. It will be interesting if the benefits of lab-made skin potentially vastly reduced animal testing laboratories garner more attention for the technique.

Photos: Tania Zbrodko / Shutterstock.com, Petrovo, Mauro, Ilic et al, courtesy Stem Cell Reports

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Human Skin Grown From Stem Cells Replicates The Real Thing ...

A study has found that it is possible to convert skin cells into the male germ cells, which are responsible for sperm production in the testes, using an established technique for creating embryonic stem cells using a form of genetic engineering.

The researchers showed that stem cells derived from human skin become active germ cells when transplanted into the testes of mice even when the man suffers from a genetic condition where he lacks functioning germ cells in his own testes.

Creating sperm-producing human cells in laboratory mice will allow scientists to study in more detail the complex sequence of events during the development if the male reproductive tissue, and to understand how these developmental changes can go awry in infertile men.

Our results are the first to offer an experimental model to study sperm development. Therefore, there is potential for applications [such as] cell-based therapies in the clinic, for example, for the generation of higher quality and numbers of sperm in a dish, said Renee Reijo Pera of Montana State University.

It might even be possible to transplant stem cell-derived germ cells directly into the testes of men with problems producing sperm, said Professor Reijo Pera, who led the study published in the journal Cell Reports. However, she emphasised that further research will be needed before clinical trials can be allowed on humans.

Although the mice had functioning human male germ cells, they did not produce human sperm, Dr Reijo Pera said. There is an evolutionary block that means that when germ cells from one species are transferred to another, there is not full spermatogenesis, unless the species are very closely related, she explained.

About one in a hundred men suffer from azoospermia, where they fail to produce measurable quantities of sperm in the semen. The condition is responsible for about 20 per cent of cases of male infertility, which itself accounts for about half of the 10-15 per cent of couples who have difficulty conceiving naturally.

The study involved creating induced pluripotent stem cells by adding key genes to the skin cells of five men three with a form of azoospermia caused by a genetic mutation on the Y chromosome and two with normal fertility. The resulting stem cells were implanted into the testes of laboratory mice where they developed normally into germ cells.

The scientists found that even the stem cells derived from the infertile men were capable to developing into human male germ cells in the mouse testes. However, the stem cells of the men with the Y chromosome mutation produced about 100 times less germ cells than the men with normal fertility, Professor Reijo Pera said.

Studying why this is the case will help us to understand where the problems are for these men and hopefully find ways to overcome them, Professor Reijo Pera said.

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New infertility treatment could grow sperm from skin cells

We put up with dry, itchy skin and are constantly applying creams to try (in vain) to fight the flake - but there might be some much needed good news for us eczema sufferers.

New research suggests eczema sufferers may have less chance of developing skin cancer.

A study conducted by experts at King's College London found the immune response triggered by eczema could stop tumours forming by shedding potentially cancerous cells.

Genetically engineered mice lacking three skin proteins - known as "knock-out" mice - were used to replicate some of the skin defects found in eczema sufferers.

Cancer-causing chemicals were tested on normal mice and the knock-out mice. Researchers found the number of benign tumours per mouse was six times lower in knock-out mice.

The new study, published in eLife, suggests both types of mice were equally susceptible to getting cancer-causing mutations, but an exaggerated inflammatory reaction in knock-out mice led to enhanced shedding of potentially cancerous cells from the skin.

Professor Fiona Watt, director of the centre for stem cells and regenerative medicine at King's College London, said: "We are excited by our findings as they establish a clear link between cancer susceptibility and an allergic skin condition in our experimental model.

"They also support the view that modifying the body's immune system is an important strategy in treating cancer.

"I hope our study provides some small consolation to eczema sufferers - that this uncomfortable skin condition may actually be beneficial in some circumstances."

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Eczema Could Reduce The Risk Of Skin Cancer, Research Shows

A new development in fertility treatment scientists have successfully produced early-stage sperm cells from the skin cells of infertile men.

According to the study, Stanford University researchers took skin cells from infertile men, turned them into stem cells known as induced pluripotent stem cellsand then implanted those cells in the tubules of mice testes. (Via Flickr / 7715592@N03,33852688@N08)

Before we move forward, you might be wondering how scientists turned skin cells back into stem cells. This video from Stem Cell Network sums up the process.

"If some adult cell types are taken, grown in plastic dishes and given specific genetic instructions, over time a small number of these cells will reverse from their differentiated state and develop the ability to redifferentiate."(Via Vimeo /Stem Cell Network)

Researchers discovered the stem cells developed into germ cells, the precursor to sperm cells. (Via YouTube / CreekValleyCritters)

But while this new development seemingly bodes well for future fertility treatment, a writer for The Guardian points out one major concern.

"The cells that lodged in the tubules developed into early-stage sperm cells, but others turned into small tumours. The danger of causing cancer in the men is one of the major risks that scientists need to overcome." (Via The Guardian)

And LiveScience reports the research is still in its infancy, noting even though the stem cells produced germ cells, they "did not go on to form mature sperm in the mice."The head researcher for the study told LiveScience this is likely because of the "evolutionary differences between humans and mice."

Despite concerns, Nature World News says this research has potential, because there are various uses for the treatment. "There is also the possibility of using cells from endangered species to help boost their reproduction."

According to the American Society for Reproductive Medicine, about 12 percentof adults suffer from infertility. The study has been published in the journal Cell Reports.

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Human skin cells used to create sperm cells

Here is a new development in fertility treatment: Scientists have successfully produced early-stage sperm cells from the skin cells of infertile men.

According to thestudy, Stanford University researchers took skin cells from infertile men, turned them into stem cells known as induced pluripotent stem cells, and then implanted those cells in the tubules of mice testes. (ViaFlickr / 7715592@N03,33852688@N08)

Before we move forward, you might be wondering how scientists turned skin cells back into stem cells. Stem Cell Networksummed up the process: "If some adult cell types are taken, grown in plastic dishes and given specific genetic instructions, over time a small number of these cells will reverse from their differentiated state and develop the ability to redifferentiate."(ViaVimeo /Stem Cell Network)

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Researchers discovered the stem cells developed into germ cells, the precursor to sperm cells. (ViaYouTube /CreekValleyCritters)

But while this new development seemingly bodes well for future fertility treatment, a writer forThe Guardianpoints out one major concern: "The cells that lodged in the (mice) tubules developed into early-stage sperm cells, but others turned into small tumors. The danger of causing cancer in the men is one of the major risks that scientists need to overcome."(ViaThe Guardian)

Despite concerns,Nature World Newssays this research has potential, because there are various uses for the treatment."There is also the possibility of using cells from endangered species to help boost their reproduction," the organization reported.

According to theAmerican Society for Reproductive Medicine, about 12 percentof adults suffer from infertility. The study has been published in the journal Cell Reports.

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Scientists use human skin to create sperm cells

Scientists have turned skin tissue from infertile men into early-stage sperm cells in a groundbreaking study that raises hopes for new therapies for the condition.

The unexpected success of the procedure has stunned some scientists, because it was thought to be impossible for the men to make any sperm.

The men who took part in the study had major genetic defects on their Y sex chromosomes, which meant they could not produce healthy adult sperm on their own.

About 1% of men cannot make any sperm, a condition known as azoospermia, while a fifth of men have low sperm counts. Male fertility is a concern for roughly half of couples who seek IVF treatment.

In the latest study, researchers took skin cells from three infertile men and converted them into stem cells, which can grow into almost any tissue in the body. When these cells were transplanted into the testes of mice, they developed into early-stage human sperm cells.

What we found was that cells from men who did not possess sperm at the time of clinical observation were able to produce the precursors for sperm, said Cyril Ramathal, of Stanford University.

Skin cells from infertile men grew into fewer early-stage sperm cells than cells taken from normally fertile men, the study found.

The research is at an early stage, but scientists suspect that the converted skin cells might have grown into mature sperm cells if they had been transplanted into the infertile mens testes.

If further work confirms the suspicion, it may be possible to restore male fertility by taking mens skin cells, turning them into stem cells, and injecting these into their testes. The same might be done for men who are left infertile after having chemotherapy for cancer.

Being able to efficiently convert skin cells into sperm would allow this group to become biologic fathers, said Michael Eisenberg, director of male reproduction and surgery at Stanford, who was not involved in the study. Infertility is one of the most common and devastating complications of cancer treatments, especially for young boys and men.

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Scientists turn tissue from infertile men into sperm cells