Archive for the ‘Skin Stem Cells’ Category

Researchers at the University of Cambridge have grown functional "mini-lungs" using stems cells derived from the skin cells of patients with a debilitating lung disease. Not only can the development help them in coming up with effective treatments for specific lung diseases like cystic fibrosis, but the process has the potential to be scaled up to screen thousands of new compounds to identify potential new drugs.

Creating miniature organoids has been the focus of many a research group, as it allows scientists to better understand the processes that take place inside an organ, figure out how specific diseases occur and develop or even work towards creating bioengineered lungs.

The research team from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute studied a lung disease called cystic fibrosis, which is caused by genetic mutation and shortens a patient's average lifespan. Patients have great difficulty breathing as the lungs are overwhelmed by thickened mucus.

To create working mini-lungs, the researchers took skin cells from patients with the most common form of cystic fibrosis and reprogrammed them to an induced pluripotent state (iPS), which allows the cells to grow into a different type of cell inside the body.

They then activated a process called gastrulation which pushes the cells to form distinct layers such as the endoderm and foregut. The cells were then pushed further to form distal airway tissue, the part of the lung that deals with exchange of gases.

In a sense, what weve created are mini-lungs," says Dr Nick Hannan, the lead researcher. While they only represent the distal part of lung tissue, they are grown from human cells and so can be more reliable than using traditional animal models, such as mice."

To find out whether the mini lungs could actually be used to screen drugs, the team tested them out with the aid of chloride-sensitive fluorescent dye. Cells from cystic fibrosis patients typically malfunction and don't allow the chloride to pass through, so there's no change in fluorescence levels.

The team added a molecule that's currently undergoing clinical trials and noted a change in fluorescence, signaling that it was effective in getting the diseased lung cells to function properly and that the mini lungs could, in principle, be used to test potential new drugs.

"Were confident this process could be scaled up to enable us to screen tens of thousands of compounds and develop mini-lungs with other diseases such as lung cancer and idiopathic pulmonary fibrosis," says Dr Hannan. "This is far more practical, should provide more reliable data and is also more ethical than using large numbers of mice for such research."

The research was published in the journal Stem Cells and Development.

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Scientists create functioning "mini-lungs" to study cystic fibrosis

Immune system response isn't as crucial as activity of the infected cells themselves

DURHAM, N.C. -- For people infected with the human papilloma virus (HPV), the likelihood of clearing the infection and avoiding HPV-related cancer may depend less on the body's disease-fighting arsenal than has been generally assumed.

A new study finds that the body's ability to defeat the virus may be largely due to unpredictable division patterns in HPV-infected stem cells, rather than the strength of the person's immune response.

If the mathematical model behind the findings holds up, it could point to ways of tweaking the way infected cells divide in order to make HPV infections go away faster and hence lower the risk of developing cancer, said co-author Marc Ryser of Duke University.

The results appear online in the journal PLOS Computational Biology.

More than six million people in the U.S. become infected with HPV every year. Most people clear the virus on their own in one to two years with little or no symptoms. But in some people the infection persists. The longer HPV persists the more likely it is to lead to cancer, including cancers of the cervix, penis, anus, mouth and throat.

To better understand why some HPV infections go away and others progress, Duke mathematicians Marc Ryser and Rick Durrett developed a model of HPV infection at the level of the infected tissue.

HPV spreads through intimate skin-to-skin contact during sex with an infected person, and takes advantage of the tissue's natural internal repair system to reproduce and spread.

The invading virus breaks through the layers of cells that line the cervix and other tissues and infects the stem cells in the innermost layer, called the basal layer.

Usually, when an infected stem cell divides into two, one of the new cells stays in the basal layer and the other cell is pushed outward into the upper layers where it dies and is sloughed off, releasing virus particles that can then infect another person.

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Why some HPV infections go away and others become cancer

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Cambridge stem cell scientists searching for new cystic fibrosis treatments have grown "mini-lungs" in a laboratory.

The millimetre-wide cell clusters were created using stem cells derived from the skin of patients with the devastating lung disease.

They are the latest in a line of 3D "organoids" produced to mimic the behaviour of specific body tissues, following "mini-brains" for studying Alzheimer's disease and "mini-livers" to model diseases of the liver.

Dr Nick Hannan, led the team from Cambridge University.

He said: "In a sense, what we've created are 'mini-lungs'.

"While they only represent the distal (outer) part of lung tissue, they are grown from human cells and so can be more reliable than using traditional animal models, such as mice.

"We can use them to learn more about key aspects of serious diseases - in our case, cystic fibrosis."

Cystic fibrosis occurs when the movement of water to the inside of the lungs is reduced, causing a build up of thick mucus that leads to a high risk of infection.

The scientists reprogrammed ordinary skin cells to create stem cells that could be transformed into lung tissue.

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Stem cell "mini-lungs" created in Cambridge University lab

New York, March 20 (IANS): High stress levels can have a critical impact not only on the surface, making our skin age, but also on a molecular level, when stressed cells cannot cope with the pressure and perish much faster than the ones which can.

In a new research report released on Thursday, scientists at the University of California, Berkeley, analysed blood stem cells and found that the cell's ability to repair damage in the mitochondria, their power source, was critical to their survival.

Researchers tried to "relax" these stressed-out cells by slowing down the activity of their mitochondria.

"We found that by slowing down the activity of mitochondria in the blood stem cells of mice, we were able to enhance their capacity to handle stress and rejuvenate old blood. This confirms the significance of this pathway in the aging process," Xinhua news agency quoted Danica Chen, an assistant professor with the Department of Nutritional Sciences and Toxicology.

This pathway lies mainly in the multitude of proteins that need to be folded properly for the mitochondria to function correctly. When the folding goes awry, the mitochondrial unfolded-protein response, or UPRmt, kicks in to boost the production of specific proteins to fix or remove the misfolded protein.

Researchers found that certain proteins known as SIRT7 help cells cope with the stress of unfolding the proteins in the mitochondria, helping those with higher levels of SIRT7 survive longer by making them "unwind". But the levels of SIRT7 decrease as people age.

"The protein level decreases as years go by," Chen said. "But if we increase this protein in blood stem cells, we can make them live longer. Cells in general don't just die suddenly; they are submitted to high stress levels and lose their functions with age."

Chen does not want to encourage the thought that she and other researchers have found the "fountain of youth", but more of a new path for study.

"We still don't know if this would work on other kinds of stem cells, such as pancreatic stem cells or heart cells, and we don't have any expertise with those tissues, so we would be very happy to collaborate with other laboratories to tackle the matter," she said.

The study, published on Thursday in the Science journal, is expected to help researchers gain more insight into the aging process, and even slow it down.

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Fountain of youth might hide in 'relaxed' stem cells: Study

Scientists at the University of Cambridge have successfully created 'mini-lungs' using stem cells derived from skin cells of patients with cystic fibrosis, and have shown that these can be used to test potential new drugs for this debilitating lung disease.

The research is one of a number of studies that have used stem cells - the body's master cells - to grow 'organoids', 3D clusters of cells that mimic the behaviour and function of specific organs within the body. Other recent examples have been 'mini-brains' to study Alzheimer's disease and 'mini-livers' to model liver disease. Scientists use the technique to model how diseases occur and to screen for potential drugs; they are an alternative to the use of animals in research.

Cystic fibrosis is a monogenic condition - in other words, it is caused by a single genetic mutation in patients, though in some cases the mutation responsible may differ between patients. One of the main features of cystic fibrosis is the lungs become overwhelmed with thickened mucus causing difficulty breathing and increasing the incidence of respiratory infection. Although patients have a shorter than average lifespan, advances in treatment mean the outlook has improved significantly in recent years.

Researchers at the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute used skin cells from patients with the most common form of cystic fibrosis caused by a mutation in the CFTR gene referred to as the delta-F508 mutation. Approximately three in four cystic fibrosis patients in the UK have this particular mutation. They then reprogrammed the skin cells to an induced pluripotent state, the state at which the cells can develop into any type of cell within the body.

Using these cells - known as induced pluripotent stem cells, or iPS cells - the researchers were able to recreate embryonic lung development in the lab by activating a process known as gastrulation, in which the cells form distinct layers including the endoderm and then the foregut, from which the lung 'grows', and then pushed these cells further to develop into distal airway tissue. The distal airway is the part of the lung responsible for gas exchange and is often implicated in disease, such as cystic fibrosis, some forms of lung cancer and emphysema.

The results of the study are published in the journal Stem Cells and Development.

"In a sense, what we've created are 'mini-lungs'," explains Dr Nick Hannan, who led the study. "While they only represent the distal part of lung tissue, they are grown from human cells and so can be more reliable than using traditional animal models, such as mice. We can use them to learn more about key aspects of serious diseases - in our case, cystic fibrosis."

The genetic mutation delta-F508 causes the CFTR protein found in distal airway tissue to misfold and malfunction, meaning it is not appropriately expressed on the surface of the cell, where its purpose is to facilitate the movement of chloride in and out of the cells. This in turn reduces the movement of water to the inside of the lung; as a consequence, the mucus becomes particular thick and prone to bacterial infection, which over time leads to scarring - the 'fibrosis' in the disease's name.

Using a fluorescent dye that is sensitive to the presence of chloride, the researchers were able to see whether the 'mini-lungs' were functioning correctly. If they were, they would allow passage of the chloride and hence changes in fluorescence; malfunctioning cells from cystic fibrosis patients would not allow such passage and the fluorescence would not change. This technique allowed the researchers to show that the 'mini-lungs' could be used in principle to test potential new drugs: when a small molecule currently the subject of clinical trials was added to the cystic fibrosis 'mini lungs', the fluorescence changed - a sign that the cells were now functioning when compared to the same cells not treated with the small molecule.

"We're confident this process could be scaled up to enable us to screen tens of thousands of compounds and develop mini-lungs with other diseases such as lung cancer and idiopathic pulmonary fibrosis," adds Dr Hannan. "This is far more practical, should provide more reliable data and is also more ethical than using large numbers of mice for such research."

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Scientists grow 'mini-lungs' to aid the study of cystic fibrosis

Scientists at the University of Cambridge have successfully created 'mini-lungs' using stem cells derived from skin cells of patients with cystic fibrosis, and have shown that these can be used to test potential new drugs for this debilitating lung disease.

The research is one of a number of studies that have used stem cells -- the body's master cells -- to grow 'organoids', 3D clusters of cells that mimic the behaviour and function of specific organs within the body. Other recent examples have been 'mini-brains' to study Alzheimer's disease and 'mini-livers' to model liver disease. Scientists use the technique to model how diseases occur and to screen for potential drugs; they are an alternative to the use of animals in research.

Cystic fibrosis is a monogenic condition -- in other words, it is caused by a single genetic mutation in patients, though in some cases the mutation responsible may differ between patients. One of the main features of cystic fibrosis is the lungs become overwhelmed with thickened mucus causing difficulty breathing and increasing the incidence of respiratory infection. Although patients have a shorter than average lifespan, advances in treatment mean the outlook has improved significantly in recent years.

Researchers at the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute used skin cells from patients with the most common form of cystic fibrosis caused by a mutation in the CFTR gene referred to as the delta-F508 mutation. Approximately three in four cystic fibrosis patients in the UK have this particular mutation. They then reprogrammed the skin cells to an induced pluripotent state, the state at which the cells can develop into any type of cell within the body.

Using these cells -- known as induced pluripotent stem cells, or iPS cells -- the researchers were able to recreate embryonic lung development in the lab by activating a process known as gastrulation, in which the cells form distinct layers including the endoderm and then the foregut, from which the lung 'grows', and then pushed these cells further to develop into distal airway tissue. The distal airway is the part of the lung responsible for gas exchange and is often implicated in disease, such as cystic fibrosis, some forms of lung cancer and emphysema.

The results of the study are published in the journal Stem Cells and Development.

"In a sense, what we've created are 'mini-lungs'," explains Dr Nick Hannan, who led the study. "While they only represent the distal part of lung tissue, they are grown from human cells and so can be more reliable than using traditional animal models, such as mice. We can use them to learn more about key aspects of serious diseases -- in our case, cystic fibrosis."

The genetic mutation delta-F508 causes the CFTR protein found in distal airway tissue to misfold and malfunction, meaning it is not appropriately expressed on the surface of the cell, where its purpose is to facilitate the movement of chloride in and out of the cells. This in turn reduces the movement of water to the inside of the lung; as a consequence, the mucus becomes particular thick and prone to bacterial infection, which over time leads to scarring -- the 'fibrosis' in the disease's name.

Using a fluorescent dye that is sensitive to the presence of chloride, the researchers were able to see whether the 'mini-lungs' were functioning correctly. If they were, they would allow passage of the chloride and hence changes in fluorescence; malfunctioning cells from cystic fibrosis patients would not allow such passage and the fluorescence would not change. This technique allowed the researchers to show that the 'mini-lungs' could be used in principle to test potential new drugs: when a small molecule currently the subject of clinical trials was added to the cystic fibrosis 'mini lungs', the fluorescence changed -- a sign that the cells were now functioning when compared to the same cells not treated with the small molecule.

"We're confident this process could be scaled up to enable us to screen tens of thousands of compounds and develop mini-lungs with other diseases such as lung cancer and idiopathic pulmonary fibrosis," adds Dr Hannan. "This is far more practical, should provide more reliable data and is also more ethical than using large numbers of mice for such research."

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Scientists grow 'mini-lungs' to aid study of cystic fibrosis

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Newswise Stem cells can have a strong sense of identity. Taken out of their home in the hair follicle, for example, and grown in culture, these cells remain true to themselves. After waiting in limbo, these cultured cells become capable of regenerating follicles and other skin structures once transplanted back into skin. Its not clear just how these stem cells and others elsewhere in the body retain their ability to produce new tissue and heal wounds, even under extraordinary conditions.

New research at Rockefeller University has identified a protein, Sox9, that takes the lead in controlling stem cell plasticity. In a paper published Wednesday (March 18) in Nature, the team describes Sox9 as a pioneer factor that breaks ground for the activation of genes associated with stem cell identity in the hair follicle.

We found that in the hair follicle, Sox9 lays the foundation for stem cell plasticity. First, Sox9 makes the genes needed by stem cells accessible, so they can become active. Then, Sox9 recruits other proteins that work together to give these stemness genes a boost, amplifying their expression, says study author Elaine Fuchs, Rebecca C. Lancefield Professor, Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development. Without Sox9, this process never happens, and hair follicle stem cells cannot survive.

Sox9 is a type of protein called a transcription factor, which can act like a volume dial for genes. When a transcription factor binds to a segment of DNA known as an enhancer, it cranks up the activity of the associated gene. Recently, scientists identified a less common, but more powerful version: the super-enhancer. Super-enhancers are much longer pieces of DNA, and host large numbers of cell type-specific transcription factors that bind cooperatively. Super-enhancers also contain histones, DNA-packaging proteins, that harbor specific chemical groups epigenetic marks that make genes they are associated with accessible so they can be expressed.

Using an epigenetic mark associated specifically with the histones of enhancers, first author Rene Adam, a graduate student in the lab, and colleagues, identified 377 of these high-powered gene-amplifying regions in hair follicle stem cells. The majority of these super-enhancers were bound by at least five transcription factors, often including Sox9. Then, they compared the stem cell super-enhancers to those of short-lived stem cell progeny, which have begun to choose a fate, and so lost the plasticity of stem cells. These two types of cells shared only 32 percent of their super-enhancers, suggesting these regions played an important role in skin cell identity. By switching off super-enhancers associated with stem cell genes, these genes were silenced while new super-enhancers were being activated to turn on hair genes.

To better understand these dynamics, the researchers took a piece of a super-enhancer, called an epicenter, where all the stem cell transcription factors bind, and they linked it to a gene that glowed green whenever the transcription factors were present. In living mice, all the hair follicle stem cells glowed green, but surprisingly, the green gene turned off when the stem cells were taken from the follicle and placed in culture. When they put the cells back into living skin, the green glow returned.

Another clue came from experiments performed by Hanseul Yang, another student in the lab. By examining the new super-enhancers that were gained when the stem cells were cultured, they learned that these new super-enhancers bound transcription factors that were known to be activated during wound-repair. When they used one of these epicenters to drive the green gene, the green glow appeared in culture, but not in skin. When they wounded the skin, then the green glow switched on.

We were learning that some super-enhancers are specifically activated in the stem cells within their native niche, while other super-enhancers specifically switch on during injury, explained Adam. By shifting epicenters, you can shift from one cohort of transcription factors to another to adapt to different environments. But we still needed to determine what was controlling these shifts.

Originally posted here:
Scientists Pinpoint Molecule That Controls Stem Cell Plasticity by Boosting Gene Expression

Experiments placed Sox9 at the crux of a shift in gene expression associated with hair follicle stem cell identity

IMAGE:Researchers made stem cells fluoresce green (at the base of hair follicles above) by labeling their super-enhancers, regions of the genome bound by gene-amplifying proteins. It appears one such protein,... view more

Credit: Laboratory of Mammalian Cell Biology and Development at The Rockefeller University/Nature

Stem cells can have a strong sense of identity. Taken out of their home in the hair follicle, for example, and grown in culture, these cells remain true to themselves. After waiting in limbo, these cultured cells become capable of regenerating follicles and other skin structures once transplanted back into skin. It's not clear just how these stem cells -- and others elsewhere in the body -- retain their ability to produce new tissue and heal wounds, even under extraordinary conditions.

New research at Rockefeller University has identified a protein, Sox9, that takes the lead in controlling stem cell plasticity. In a paper published Wednesday (March 18) in Nature, the team describes Sox9 as a "pioneer factor" that breaks ground for the activation of genes associated with stem cell identity in the hair follicle.

"We found that in the hair follicle, Sox9 lays the foundation for stem cell plasticity. First, Sox9 makes the genes needed by stem cells accessible, so they can become active. Then, Sox9 recruits other proteins that work together to give these "stemness" genes a boost, amplifying their expression," says study author Elaine Fuchs, Rebecca C. Lancefield Professor, Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development. "Without Sox9, this process never happens, and hair follicle stem cells cannot survive."

Sox9 is a type of protein called a transcription factor, which can act like a volume dial for genes. When a transcription factor binds to a segment of DNA known as an enhancer, it cranks up the activity of the associated gene. Recently, scientists identified a less common, but more powerful version: the super-enhancer. Super-enhancers are much longer pieces of DNA, and host large numbers of cell type-specific transcription factors that bind cooperatively. Super-enhancers also contain histones, DNA-packaging proteins, that harbor specific chemical groups -- epigenetic marks -- that make genes they are associated with accessible so they can be expressed.

Using an epigenetic mark associated specifically with the histones of enhancers, first author Rene Adam, a graduate student in the lab, and colleagues, identified 377 of these high-powered gene-amplifying regions in hair follicle stem cells. The majority of these super-enhancers were bound by at least five transcription factors, often including Sox9. Then, they compared the stem cell super-enhancers to those of short-lived stem cell progeny, which have begun to choose a fate, and so lost the plasticity of stem cells. These two types of cells shared only 32 percent of their super-enhancers, suggesting these regions played an important role in skin cell identity. By switching off super-enhancers associated with stem cell genes, these genes were silenced while new super-enhancers were being activated to turn on hair genes.

To better understand these dynamics, the researchers took a piece of a super-enhancer, called an epicenter, where all the stem cell transcription factors bind, and they linked it to a gene that glowed green whenever the transcription factors were present. In living mice, all the hair follicle stem cells glowed green, but surprisingly, the green gene turned off when the stem cells were taken from the follicle and placed in culture. When they put the cells back into living skin, the green glow returned.

Another clue came from experiments performed by Hanseul Yang, another student in the lab. By examining the new super-enhancers that were gained when the stem cells were cultured, they learned that these new super-enhancers bound transcription factors that were known to be activated during wound-repair. When they used one of these epicenters to drive the green gene, the green glow appeared in culture, but not in skin. When they wounded the skin, then the green glow switched on.

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Scientists pinpoint molecule that switches on stem cell genes

(Source: Thinkstock; art by Tanya Leigh Washington)

We're no strangerswhen it comes to wild beauty products. Snail venom, check. Probiotic bacteria, of course. Charcoal, yes, please. But when we started noticing stem cells popping up as ingredients in beauty products, we raised an eye brow.

First off, these aren't the stem cells that have caused a lot of controversy in recent years. These are (typically) stem cells extracts from plants andfruits and are believed by some to encourage cell regeneration, restoration and repair. However, some products are using human stem cell derived proteins as active ingredients. The basic idea is this:stem cell extracts uppotential growth for collagen and elastinyou know, those tissues that keep us looking youthful.

Althoughthe jury is still out on the effectiveness of stem cell-based products, one thing's for surethispossible fountain of youth comes at a steep price tag. Due to the extraction and cultivation process of stem cell extracts, products tend to be on the higher end side.

If stem cell technology sounds like something you're ready to invest in, take a peek at a view of the products on the market that caught our eyes.

Rodial Stemcell Super-Food Cleanser, $40, atus.spacenk.com

Stem cell technology from thePhytoCellTec Alp Rose mixed with Coconut Oil, Rose Hip Oil, Rose Wax and Cocoa Butter hydrate and cleanses.

Juice Beauty Stem Cellular Lifting Neck Cream, $55, atjuicebeauty.com

This blend of fruit stem cells are infused into a Vitamin C, resveratrol rich grapeseed formula to provide antioxidant protection and firm up skin.

StemologyCell Revive Smoothing Serum, $99, at stemologyskincare.com

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Why Stem Cell Beauty Products are Causing a Buzz in Anti-Aging

Stem cells are special cells that can turn into any kind of cells in the body. They serve as a repair system for the body. There are two main types of human stem cells: embryonic stem cells and adult stem cells.

Embryonic stem cells are cells that come from an unborn baby (embryo). Those are NOT the cells that are used for this product.LUMINESCEformulation uses technology derived from the study of Adult Stem Cells.

Stem cells communicate with tissue cells to induce repair. They produce many different growth factors and "communication" chemicals to do this.Dr Nathan Newmanhas been able to take stem cells in the lab, and separate them from the solution that holds the growth factors. This media is the foundation of theLUMINESCEproduct.

What is the relationship between growth factors and the stem cell technology?

The patent-pending technology ofLUMINESCEprovides for the delivery of key growth factors found in natural skin. As we age, the production of these growth factors within skin is reduced, and leads to wrinkling and thinning of the skin. By re-introducing these factors through the daily application ofLUMINESCE, damaged skin cells may be repaired, and skin tissue re-generated.

Stem cells are cells that have the ability to grow into any kind of cell in the body, and they rely on special signals to tell them what cells they will ultimately become. If you know the stem cell language, then you could communicate to the cells.

In this way, you could have stem cells that become new young skin cells, rebuild collagen, and deliver a new younger looking skin.

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Stem Cells, Skin Care and Dr Newman | Skin Care

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Newswise Researchers at the University of California, San Diego School of Medicine have identified a gene variant that may be used to predict people most likely to respond to an investigational therapy under development for Alzheimers disease (AD). The study, published March 12 in Cell Stem Cell, is based on experiments with cultured neurons derived from adult stem cells.

Our results suggest that certain gene variants allow us to reduce the amount of beta amyloid produced by neurons, said senior author Lawrence Goldstein, PhD, director of UC San Diego Sanford Stem Cell Clinical Center and UC San Diego Stem Cell Program. This is potentially significant for slowing the progression of Alzheimers disease. AD is the most common cause of dementia in the United States, afflicting one in nine people age 65 and older.

The genetic risk factor investigated are variants of the SORL1 gene. The gene codes for a protein that affects the processing and subsequent accumulation of beta amyloid peptides, small bits of sticky protein that build up in the spaces between neurons. These plaques are linked to neuronal death and related dementia.

Previous studies have shown that certain variants of the SORL1 gene confer some protection from AD, while other variants are associated with about a 30 percent higher likelihood of developing the disease. Approximately one-third of the U.S. adult population is believed to carry the non-protective gene variants.

The studys primary finding is that variants in the SORL1 gene may also be associated with how neurons respond to a natural compound in the brain that normally acts to protect nerve cell health. The protective compound, called BDNF, short for brain-derived neurotrophic factor, is currently being investigated as a potential therapy for a number of neurological diseases, including AD, because of its role in promoting neuronal survival.

For the study, UC San Diego researchers took skin cells from 13 people, seven of whom had AD and six of whom were healthy control subjects, and reprogrammed the skin cells into stem cells. These stem cells were coaxed to differentiate into neurons, and the neurons were cultured and then treated with BDNF.

The experiments revealed that neurons that carried disease-protective SORL1 variants responded to the therapy by reducing their baseline rate of beta amyloid peptide production by, on average, 20 percent. In contrast, the neurons carrying the risk variants of the gene, showed no change in baseline beta amyloid production.

BDNF is found in everyones brain, said first author Jessica Young, PhD, a postdoctoral fellow in the Goldstein laboratory. What we found is that if you add more BDNF to neurons that carry a genetic risk factor for the disease, the neurons dont respond. Those with the protective genetic profile do.

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Boosting A Natural Protection Against Alzheimer's Disease

March 12, 2015 // R. Colin Johnson

Living beating hearts on-a-chip were recently created from pluripotent stem cells discovered by 2010 Kyoto Prize Winner, Shinya Yamanaka.

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Bioengineers at the University of Berkeley aim to create all of the human organs on-a-chip then connect them with micro-fluidic channels to create a complete human-being on-a-wafer.

"We have learned how to derive almost any type of human tissue from skin stem cells as was first discovered by Yamanaka," professor Kevin Healy told EE Times. "Our initial application is drug screening without having to use animals, but putting organs-on-a-chip using the stem cells of the patient could help with genetic diseases as well."

"For instance, one drug might solve a heart problem, but create toxins in the liver," Healy told us. "Which would be much better to find out before administering to the patient."

As to creating living robots in this way, Healy said that was not their mission on the current project, since their funding in coming from the National Institutes of Health's (NIH's) Tissue Chip for Drug Screening Initiative, an interagency collaboration specifically aimed at developing 3-D human tissue chips for drug screening.

However, the technology being creating, especially the microfluidic channels connecting the organs-on-a-chip so that they interact, could someday serve as a basis for making robot-like creatures.

"What we would need for that is sensors and actuators. Sensors would be the easiest, but MIT in particular is working on artificial muscles to serve as actuators," Healy told us.

Living beating hearts on-a-chip were recently created from pluripotent stem cells discovered by 2010 Kyoto Prize Winner, Shinya Yamanaka.

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Heart on-a-chip beats

Testing breast cancer cells for how closely they resemble stem cells could identify women with the most aggressive disease, a new study suggests.

Researchers found that breast cancers with a similar pattern of gene activity to that of adult stem cells had a high chance of spreading to other parts of the body.

Assessing a breast cancer's pattern of activity in these stem cell genes has the potential to identify women who might need intensive treatment to prevent their disease recurring or spreading, the researchers said.

Adult stem cells are healthy cells within the body which have not specialised into any particular type, and so retain the ability to keep on dividing and replacing worn out cells in parts of the body such as the gut, skin or breast.

A research team from The Institute of Cancer Research, London, King's College London and Cardiff University's European Cancer Stem Cell Research Institute identified a set of 323 genes whose activity was turned up to high levels in normal breast stem cells in mice.

The study is published today (Wednesday) in the journal Breast Cancer Research, and was funded by a range of organisations including the Medical Research Council, The Institute of Cancer Research (ICR), Breakthrough Breast Cancer and Cancer Research UK.

The scientists cross-referenced their panel of normal stem cell genes against the genetic profiles of tumours from 579 women with triple-negative breast cancer - a form of the disease which is particularly difficult to treat.

They split the tumour samples into two categories based on their 'score' for the activity of the stem cell genes.

Women with triple-negative tumours in the highest-scoring category were much less likely to stay free of breast cancer than those with the lowest-scoring tumours. Women with tumours from the higher-scoring group had around a 10 per cent chance of avoiding relapse after 10 years, while women from the low-scoring group had a chance of around 60 per cent of avoiding relapse.

The results show that the cells of aggressive triple-negative breast cancers are particularly 'stem-cell-like', taking on properties of stem cells such as self-renewal to help them grow and spread. They also suggest that some of the 323 genes could be promising targets for potential cancer drugs.

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'Stem cell' test could identify most aggressive breast cancers

Babies with two fathers or two mothers could soon become a reality Egg and sperm cells can be made using skin from two same sex adults Scientists say technique could be used to create baby two years from now Breakthrough could help infertile or gay couples to have children But concerns have been raised about prospect of 'designer babies'

By Ben Spencer for the Daily Mail

Published: 20:21 EST, 22 February 2015 | Updated: 20:22 EST, 22 February 2015

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Babies with two fathers or two mothers could become a reality after a breakthrough by researchers at Cambridge.

They have shown that it is possible to make human egg and sperm cells using skin from two adults of the same sex.

The development could help men and women who have become infertile through disease or gay couples to have children.

But critics voiced concern, arguing that the breakthrough brings closer the prospect of 'designer babies', in which the looks, character and health attributes of children would be selected by parents.

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Scientists say they can make human egg from skin of two men

IMAGE:This is Assistant Professor of Biology Jason Meyer, Ph.D. of the School of Science at Indiana University-Purdue University Indianapolis with graduate students Sarah Ohlemacher (left) and Akshaya Sridhar. view more

Credit: School of Science at Indiana University-Purdue University Indianapolis

INDIANAPOLIS -- Jason Meyer, Ph.D., assistant professor of biology in the School of Science at Indiana University-Purdue University Indianapolis, has received a National Institutes of Health grant to study how glaucoma develops in stem cells created from skin cells genetically predisposed to the disease. The five-year, $1.8 million grant is funded by the NIH's National Eye Institute.

Glaucoma is a group of degenerative diseases that damage the eye's optic nerve and can result in vision loss and blindness. It is the most common disease that affects retinal ganglion cells. These cells serve as the connection between the eye and the brain. Once these cells are damaged or severed, the brain cannot receive critical information, leading to blindness.

Meyer's research uses human induced pluripotent stem cells, which can be generated from any cell in the body. In this case, they are created from skin cells of patients predisposed to glaucoma. These cells are genetically reprogrammed and then given instructions to develop into cells of the eye's retina.

"Our hope is that because these cells have the genetic information to develop the disease, they will do so in our lab," Meyer said. "Hopefully, we can figure out what goes wrong in those cells and then develop new ways to fix that."

Meyer and two School of Science graduate students are now creating the stem cells and observing their features to determine what isn't going the way it should. They will determine whether they can identify the cause of damage or death of the retinal ganglion cells.

"This is a five-year award, so our hope is that toward the end of the award we can use the information we gather to start developing customized strategies to fix what's going wrong," Meyer said.

He sees this as an exciting approach to stem cell research. Often, stem cells are transplanted to replace cells damaged by disease. While that's a possibility, Meyer's research instead could lead to repairing the existing cells in the eye and restoring vision for patients.

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IUPUI biologist receives NIH grant to study how glaucoma develops in stem cells

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Come back Frankenstein all is forgiven. Scientists say they are close to manufacturing a baby in a dish from stem cells taken from the skin of two males. Why?

The human race has been producing babies the natural way since the beginning.

Why cant they use their skills to find cures to all the diseases that continue to plague us?

I have every sympathy for those who cant produce children of their own but there are plenty of needy babies awaiting adoption.

The last thing this world needs is more babies.

It is producing far too many already. Over-population will pose a bigger threat to this planet than anything else, unless it is brought under control.

But when I see how impossible it is for nations to agree on other serious issues that affect this world I hold little or no hope for a solution to that problem.

Terry Hillier, Four Crosses

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Letter: Leave babies up to nature

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Newswise In a study published today (February 26) in Cell, researchers at Rockefeller University home in on one culprit that fuels this variable vulnerability within squamous cell cancers: exposure to a signal known as TGF-, given off by immune cells that congregate next to a tumors blood vessels.

There are several reasons why some cancer stem cells, the cells at the root of tumors and metastases, can withstand therapy meant to eradicate them. Our results point to the importance of the environment immediately surrounding the skin cancer stem cells, specifically, their exposure to the signal TGF-, says senior researcher Elaine Fuchs, Rebecca C. Lancefield Professor, head of the http://Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Developmenthttp://lab.rockefeller.edu/fuchs/ and a Howard Hughes Medical Institute Investigator. Ultimately, we hope this new insight could lead to better means for preventing the recurrence of these life-threatening cancers, which can occur in the skin, head, neck, esophagus, and lung, and often evade treatment.

Her team, which included first author Naoki Oshimori, a postdoctoral research associate in the lab and lab technician Daniel Oristian, focused on squamous cell carcinomas in the skin of mice. Like many normal tissue stem cells, the stem cells that produce squamous cell tumors can be classified into two types: those that divide and proliferate rapidly, and those that do so more slowly. This has led scientists to wonder whether the more dormant stem cells in a tumor might evade cancer drugs.

To investigate this possibility, the team zeroed in on TGF- (transforming growth factor beta) which is known to restrict growth in many healthy tissues. The labs previous research has shown that mice whose normal skin stem cells cannot respond to TGF- become susceptible to develop tumors that grow rapidly. Paradoxically, however, TGF- contributes to metastasis in many cancers. The researchers wanted to know: How can TGF- act both to suppress cancers and promote them?

By visualizing TGF- signaling within developing mouse tumors, the researchers found that the cancer stem cells located nearest to the blood vessels of the tumor receive a strong TGF- signal, while others further away dont receive any. To see this difference and its effects, they used a red tag to illuminate those cells exposed and responding to TGF-, and a green genetic tag, which they could switch on, to track the stem cells progeny. Over time, they saw that TGF--responding stem cells proliferate more slowly but they simultaneously invade, scatter and move away from the tumor. The opposite was true of cancer stem cells too far away to receive TGF-, which proliferated rapidly, but were less invasive, growing as a tumor mass.

We tested the implications for drug resistance by injecting cisplatin, a commonly used chemotherapy drug for these types of cancers, into the mice with tumors. While the drug killed off most of the TGF- nonresponding cancer cells, it left behind many of the responders, Oshimori says. When the drug was withdrawn, the lingering TGF- responding cancer stem cells grew back the tumor.

We found that the TGF- heterogeneity in the tumor microenvironment produces some cancers stem cells that divide rapidly and lead to accelerated tumor growth, and other cancer stem cells that invade surrounding healthy tissue and escape cancer therapies, Fuchs explains. Moreover, conventional wisdom might say that a leisurely pace of cell division, like that seen in the TGF- responders, makes it possible for these cells to circumvent anticancer treatments that target rapidly dividing cells. While this may be true for some types of anticancer drugs, we found changes in antioxidant activity in these cells are more important for their resistance to cisplatin.

Indeed, when the team compared the genes expressed by the TGF- responders with those of the nonresponders, they found highly elevated expression in a battery of genes encoding enzymes involved in making and utilizing glutathione, an important antioxidant and detoxifying substance in cells. This unexpected finding led the team to test the impact of glutathione metabolism and conclude this metabolic pathway prevents TGF- responders from critical damage by anti-cancer drugs as well as oxidative stresses.

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Growth Signal Can Influence Cancer Cells' Vulnerability to Drugs, Study Suggests

A team of European researchers has devised a strategy to ensure that adult epidermal stem cells are safe before they are used as treatments for patients. The approach involves a clonal strategy where stem cells are collected and cultivated, genetically modified and single cells isolated before being rigorously tested to make sure they meet the highest possible safety criteria. The strategy, which is published online in EMBO Molecular Medicine, is inspired by the approaches the biotechnology industry and regulatory affairs authorities have adopted for medicinal proteins produced from genetically engineered mammalian cells.

"Until now there has not been a systematic way to ensure that adult epidermal stem cells meet all the necessary requirements for safety before use as treatments for disease," says EMBO Member Yann Barrandon, Professor at Lausanne University Hospital, the Swiss Federal Institute of Technology in Lausanne and the lead author of the study. "We have devised a single cell strategy that is sufficiently scalable to assess the viability and safety of adult epidermal stem cells using an array of cell and molecular assays before the cells are used directly for the treatment of patients. We have used this strategy in a proof-of-concept study that involves treatment of a patient suffering from recessive dystrophic epidermolysis bullosa, a hereditary condition defined by the absence of type VII collagen which leads to severe blistering of the skin."

The researchers cultivated epidermal cells from the patient that can be used to regenerate skin. The scientists used their array of tests to determine which of the transduced cells met the necessary requirements for stemness -- the characteristics of a stem cell that distinguish it from a regular cells -- and safety. Clonal analysis revealed that the transduced stem cells varied in their ability to produce functional type VII collagen. When the most viable, modified stem cells were selected, transplantation onto immunodeficient mice regenerated skin that did not blister in the mouse model system for recessive dystrophic epidermolysis bullosa and produced functional type VII collagen. Safety was assessed by determining the sites of integration of the viral vector, looking for rearrangements and hit genes, as well as whole genome sequencing.

"Our work shows that at least for adult epidermal stem cells it is possible to use a clonal strategy to deliver a level of safety that cannot be obtained by other gene therapy approaches. A clonal strategy should make it possible to integrate some of the more recent technologies for targeted genome editing that offer more precise ways to change genes in ways that may further benefit the treatment of disease. Further work is in progress in this direction."

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The above story is based on materials provided by EMBO - excellence in life sciences. Note: Materials may be edited for content and length.

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Quality control for adult stem cell treatment

February 25, 2015

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Chuck Bednar for redOrbit.com @BednarChuck

Scientists from the UK and Israel have demonstrated for the first time that it is possible to make human egg and sperm cells using skin from two adults of the same sex a breakthrough that may make it possible for same-sex couples to have children with shared DNA.

The research, which was funded by the Wellcome Trust, was completed at Cambridge University with the assistance of experts from the Weizmann Institute of Science, Cambridge News reported on Monday. They were able to use stem cell lines from embryos and from five different adults (a total of 10 different donor sources) to successfully create germ-cell lines.

According to CBS Atlanta, the experiment had previously been successful in creating live baby mice, but this new study marks the first time in which engineered human cells were found to be an identical match to aborted fetuses. It also marks the first time that human stem and skin cells were combined to form entirely new germ-cell lines.

[STORY: FDA reconsidering ban on homosexual, bisexual blood donors]

We have succeeded in the first and most important step of this process, which is to show we can make these very early human stem cells in a dish, Azim Surani, project leader at the Wellcome Trust and a professor of physiology and reproduction at Cambridge, told The Sunday Times.

Hope for those who cant conceive

The key to the process was SOX17, a master gene which typically works to direct stem cells to form whatever type of tissue or organ is required. Their new process works by manipulating this gene so that it becomes part of a primordial germ cell specification (causing it to create cells that will form an entire person), making it possible to create primordial germ cells in the lab.

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Sperm and egg created from skin cells of two same sex adults

While well known for its unique electromechanical properties, graphene may also prove key in preventing cancer tumor recurrence. A drawback of traditional cancer treatment with radiation and chemotherapy is that the primary developmental source of future tumors is not eradicated. Cancer stem cells, or CSCs, can survive treatment and give rise to recurring tumors, metatasis, and drug resistance after repeated treatments. Researchers from the University of Manchester and the University of Calabria have discovered that graphene oxides targets and neutralize CSCs in a manner that is not yet fully understood.

One CSC can develop into a ball of new CSCs called a tumor-sphere, or into new tumor cells, such as what happens in metastasis. They're immortal, divide rapidly, and resist stress. A potential solution? Graphene oxide, GO, which is an oxidized form of its well-known carbon cousin and soluble in many solvents.

For a complete look at the efficacy of GO across cancers, researchers used CSCs from six types of cancer: breast, pancreatic, lung, brain, ovarian and prostate. They also used normal skin cells to confirm that GO would not be toxic to the body.

After cells were treated for 48 hours with a GO solution, the researchers found that not only did GO interrupt the ability of CSCs in all cancer types to proliferate by forming spheres, but that GO was safe to the skin cells.

Dr Aravind Vijayaraghavan of the National Graphene Institute at the University of Manchester says that GO seems to force the cancer stem cells to differentiate into non-cancer stem cells. In this way, GO effectively takes the CSC out of commission for creating future tumors. Currently the theory is that GO interferes with the signalling pathways in the cell membranes, curbing the proliferation mechanism.

Interestingly, this graphene derivative had already been researched for as a targeted delivery vehicle in tumors, but has now been found to have an important effect itself on the tumor.

While the researchers acknowledge that the mechanisms at play need to be researched more before the material can be used to treat cancers, the ability to destroy cancer stem cells is an an important component of a cancer treatment protocol that kills existing tumors as well as shuts down future metatasis.

Vijayaraghavan and the Graphene Institute have previously made headlines as a recipient of research money from the Bill and Melinda Gates Foundation towards the development of a better condom. Their proposal, of course, used graphene.

The team's research was originally published in Oncotarget on February 24, 2015.

Source: University of Manchester

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Graphene derivative interferes with seemingly invincible cancer stem cells

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A stem cell research breakthrough might someday allow same-sex couples to have their own biological children.

Researchers at Cambridge University in England have taken the first steps towards creating artificial sperm and eggs by reprogramming skin cells from adults and converting them into embryonic-like stem cells. The team then compared the engineered stem cells with human cells from fetuses to confirm they were in fact, identical.

The researchers published their findings in the journal Cell earlier this week, stressing that its early days for this type of research.

We have succeeded in the first and most important step of the process, Dr. Jacob Hanna, an investigator with the Weizmann Institute of Science in Israel, told ABC News.

Hanna said the team will now attempt to complete the process by creating fully developed artificial sperm and eggs, either in a dish or by implanting them in a rodent. Once this is achieved, the technique could become useful for any individual with fertility problems, he said, including couples of the same sex.

"It has already caused interest from gay groups because of the possibility of making egg and sperm cells from parents of the same sex," Hanna said.

However, the prospect of creating a baby by these artificial means alone is probably a long way off, Hanna said.

It is really important to emphasize that while this scenario might be technically possible and feasible, it is remote at this stage and many challenges need to be overcome, he said. Further, there are very serious ethical and safety issues to be considered when and if such scenarios become considered in the distant future.

The research was funded by the Wellcome Trust and the Britain Israel Research and Academic Exchange Partnership.

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The Reason Same-Sex Couples May One Day Have Biological Kids

Durham, NC (PRWEB) February 25, 2015

A new study published in the latest issue of STEM CELLS Translational Medicine reveals how a particular type of stem cell generated from fat tissue may outperform other types of stem cells in speeding up the healing of wounds caused by type 1 diabetes. In the study, ulcers in a mice model treated with these cells healed significantly faster than those treated with general types of stem cells.

Slow-healing wounds present one of the most common and perplexing complications associated with both type 1 and type 2 diabetes. If left untreated, they can lead to amputation, and even death. In fact, diabetes is the leading cause of non-traumatic lower limb amputation in the United States, according to the American Diabetes Association. Despite this, there are very few consistently effective treatments for speeding the wound-healing process in patients.

Addressing this issue, researchers at the University of Tokyo (UT) School of Medicine partnered with colleagues at the Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology (Ibaraki, Japan) to test whether a type of mesenchymal stem cell (MSC) called Muse, which is harvested from adult adipose tissue (that is, fat), might work better than other types of MSCs in treating diabetes wounds. Previous studies had shown that Muse which stands for multilineage differentiating stress-enduring cells do not have high proliferative activity, but they do generate multiple cell types of the three germ layers without inducing unfavorable tumors. Thus, Muse cells appear to be safer than other induced pluripotent or multipotent cells and might have better therapeutic potential than general (non-Muse) MSCs.

The study details how researchers isolated the Muse cells from human tissue and then injected them into skin ulcers in diabetic mice. Study leader Kotaro Yoshimura, M.D., of UTs Department of Plastic Surgery said that, After 14 days the mice treated with Muse-rich cells showed significantly accelerated wound healing compared to those treated with Muse-poor cells. The transplanted cells were integrated into the regenerated skin as vascular endothelial cells and other cells. However, they were not detected in the surrounding intact regions.

In fact, not only had the wounds of the mice treated with the Muse cells completely healed after the 14-day period, but the healed skin was thicker than that of the non-Muse treated wounds, too.

Were not sure yet why the Muse cells seem to work better, Dr. Yoshimura stated, but they expressed upregulated pluripotency markers and some angiogenic growth factors, and our animal results certainly suggest a clinical potential for them in the future. These cells can be achieved in large amounts with minimal morbidity and could be a practical tool for a variety of stem cell-depleted or ischemic conditions of various organs and tissues.

Fat tissue has been gaining attention as a practical source of adult stem cells, said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. This study suggests the future clinical potential for Muse cells.

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The full article, Therapeutic Potential of Adipose-Derived SSEA-3-Positive Muse Cells for Treating Diabetic Skin Ulcers, can be accessed at http://www.stemcellstm.com.

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Researchers Hone in on Stem Cell that Speeds Healing of Stubborn Diabetes Wounds