New research reveals that a low-calorie diet rejuvenates the biological clock in a powerful manner, keeping the body younger.

Scientists have determined that a diet low in calories facilitates the energy-regulating processes. A low-calorie diet also helps to keep the body younger. These results were recently outlined in Cell. The finding is attributable to scientists at the University of California at Irvine's Center for Epigenetics and Metabolism. The team of scientists has revealed the manner in which the body's circadian rhythms alter due to the aging process. These rhythms are the body's biological clock. The circuit controlled by the clock directly connectedto aging is centered on the efficient metabolism of energy in cells.

About the Study

The group of scientists used mice for their study. These mice were tested at six months and at 18 months of age. Tissue samples were taken from their livers. This isthe organ that serves as the interface between food intake and energy distribution within the body. Energy is metabolized in cells in accordance with nuanced circadian controls.

Findings

The scientists determined the 24-hour cycle of the older mice's metabolic systems stayed the same. There were significant changes in the circadian mechanism that triggers genes on and off according to the usage of energy within cells. This means older cells process energy in an inefficient manner. The mechanism works quite well in young mice but shuts off in older mice.

A second group of older mice was provided with a diet containing 30 percent fewer calories. This intake period lasted half a year. Energy processing in the cells ended up more than unchanged. Caloric restriction functions through a rejuvenation of the biological clock. Inthe context of the study, good aging is the result of a good clock.

Collaboration for Confirmation

A companion study outlined in Cell explains the work performed by a group of researchers from the Barcelona Institute for Research in Biomedicine. These researchers collaborated with the team described above to gauge body clock functionality in stem cells from the muscle and skin of young and old mice. They determined a diet low in calories conserved the majority of rhythmic functions that occur during youth. This is the additional proof needed to show a low-calorie diet significantly contributes to the prevention of the aging process's effects. It is important to keep the stem cells' rhythm young as these cells will function to renew and preserve day-night tissue cycles.

Consuming less food seems to ward off tissue aging. As a result, stem cells do notreprogram circadian activities. Thestudies described above are important as they help explain why low-calorie diets slow aging in mice. The same results might hold true for human beings.

The Study's Importance

Prior fruit fly studies have shown diets low in calories boost longevity. However, the research described above is the first to show caloric restriction impacts circadian rhythms' impact on cell aging. These studies reveal the cell path through which the aging process is controlled. The findings serve as an introduction as to how the elements of aging can be controlled in terms of pharmacology.

What's Next?

The scientists involved in these studies are adamant it is necessary to continue examining why metabolism produces a dominant effect on stem cell aging. When the link that delays or promotes aging has been pinpointed, treatments must be developed to regulate the link.

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A Low-Calorie Diet Slows Aging - Anti Aging News

When the sequence of the human genome was published in 2001 it was hailed as a great achievement. But now we know our genomes are much more (and much more mysterious) than a simple linear sequence of nucleotide letters. It coils around and over itself in ways that seem mindbogglingly complex. But recently researchers have begun to unravel this mystery and realize that dynamic changes in the genomes three-dimensional structure affect how and when important genes are expressed.

Now dermatologist Paul Khavari, MD, PhD, and graduate student Adam Rubin, former graduate student Brook Barajas, PhD, and researcher Mayra Furlan-Magaril, PhD, have used new mapping techniques to peer into the deepest recesses of tissue-specific stem cells progenitor cells that hang out in specialized tissues like muscle waiting for the call to divide and specialize. They identified two types of DNA contacts that help these cells answer a call to action. They published their resultsin Nature Genetics.

As Khavari explained to me in an email:

How the human genome rearranges itself to express genes needed for specific processes, such as stem cell differentiation, has been a mystery. This work shows that this not only involves physically changing DNA contacts, but also functionally activating contacts between pieces of DNA that were already established.It revises our understanding of the genome to a more living, breathing, moving entity that literally reconfigures itself as it changes its expression rather than a static template that is merely copied.

Specifically, Khavari and his colleagues found that the transformation from a tissue-specific stem cell into a more specialized cell (a process called differentiation) involves a two-step process: First the genomes of stem cells are prepped through a looping process that brings functional parts of the genome into close contact. Then the cells bide their time until the moment of differentiation, when proteins called transcription factors are unleashed to bind to these new DNA neighbors and stimulate the expression of genes necessary to launch the coming transformation.

As Khavari said:

This research illuminates a fundamental mechanism of genome regulation that has not been appreciated before. Specifically, a stem cell is pre-wired with established contacts to express a specific set of differentiation genes but only activates them when the dynamic loops are engaged. By analogy with a race, the runners are all at the starting line and ready to run in that particular event but only the firing of the gun sets the specific event in motion.

This pre-wiring not only allows the stem cells to respond quickly to differentiation signals, but it also locks them into a specific fate, the researchers believe. In this way, a muscle stem cell avoids any missteps that could result in it mistakenly becoming a skin or a blood cell rather than a muscle cell. Interestingly, the researchers also found clues suggesting that perturbations in this looping process are sometimes associated with the development of certain diseases, including skin cancer and psoriasis.

Previously: Inducible loops enable 3D gene expression studies, The quest to unravel complex DNA structures gets a boost from new technology and NIH fundingand DNA origami: How our genomes foldPhoto by Braden Collum

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Genome architecture guides stem cell fate, Stanford researchers find - Scope (blog)

Mirabai Vogt-James

Newswise UCLA researchers have discovered a new way to activate the stem cells in the hair follicle to make hair grow. The research, led by scientists Heather Christofk and William Lowry, may lead to new drugs that could promote hair growth for people with baldness or alopecia, which is hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy treatment.

The researchwas publishedin the journal Nature Cell Biology.

Hair follicle stem cells are long-lived cells in the hair follicle; they are present in the skin and produce hair throughout a persons lifetime. They are quiescent, meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases they fail to activate, which is what causes hair loss.

In this study, Christofk and Lowry, ofEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, found that hair follicle stem cell metabolism is different from other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce metabolites. As hair follicle stem cells consume the nutrient glucose a form of sugar from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can either send pyruvate to their mitochondria the part of the cell that creates energy or can convert pyruvate into another metabolite called lactate.

Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate, and if that would activate the cells and grow hair more quickly, said Christofk, an associate professor of biological chemistry and molecular and medical pharmacology.

The research team first blocked the production of lactate genetically in mice and showed that this prevented hair follicle stem cell activation. Conversely, in collaboration with the Rutter lab at University of Utah, they increased lactate production genetically in the mice and this accelerated hair follicle stem cell activation, increasing the hair cycle.

Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells, said Lowry, a professor of molecular, cell and developmental biology. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.

The team identified two drugs that, when applied to the skin of mice, influenced hair follicle stem cells in distinct ways to promote lactate production. The first drug, called RCGD423, activates a cellular signaling pathway called JAK-Stat, which transmits information from outside the cell to the nucleus of the cell. The research showed that JAK-Stat activation leads to the increased production of lactate and this in turn drives hair follicle stem cell activation and quicker hair growth. The other drug, called UK5099, blocks pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice.

Through this study, we gained a lot of interesting insight into new ways to activate stem cells, said Aimee Flores, a predoctoral trainee in Lowrys lab and first author of the study. The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think weve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; Im looking forward to the potential application of these new findings for hair loss and beyond.

The use of RCGD423 to promote hair growth is covered by a provisional patent application filed by the UCLA Technology Development Group on behalf of UC Regents. The use of UK5099 to promote hair growth is covered by a separate provisional patent filed by the UCLA Technology Development Group on behalf of UC Regents, with Lowry and Christofk as inventors.

The experimental drugs described above were used in preclinical tests only and have not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

The research was supported by the California Institute for Regenerative Medicine training grant, a New Idea Award from the Leukemia Lymphoma Society, the National Cancer Institute (R25T CA098010), the National Institute of General Medical Sciences (R01-GM081686 and R01-GM0866465), the National Institutes of Health (RO1GM094232), an American Cancer Society Research Scholar Grant (RSG-16-111-01-MPC), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5R01AR57409), a Rose Hills Foundation Research Award and the Gaba Fund; the Rose Hills award and the Gaba Fund are administered through the UCLA Broad Stem Cell Research Center.

Further research on the use of UK5099 is being funded by the UCLA Technology Development Group through funds fromCalifornia State Assembly Bill 2664.

Read more:
UCLA Scientists Identify a New Way to Activate Stem Cells to Make Hair Grow - Newswise (press release)

A novel device that reprograms skin cells could represent a breakthrough in repairing injured or aging tissue, researchers say. The new technique, called tissue nanotransfection, is based on a tiny device that sits on the surface of the skin of a living body. An intense, focused electric field is then applied across the device, allowing it to deliver genes to the skin cells beneath it -- turning them into different types of cells.

That, according to the researchers, offers an exciting development when it comes to repairing damaged tissue, offering the possibility of turning a patient's own tissue into a "bioreactor" to produce cells to either repair nearby tissues, or for use at another site.

"By using our novel nanochip technology, injured or compromised organs can be replaced," said Chandan Sen [pictured above], from the Ohio State University, who co-led the study. "We have shown that skin is a fertile land where we can grow the elements of any organ that is declining."

The ability for scientists to reprogram cells into other cell types is not new: the discovery scooped John Gurdon and Shinya Yamanaka the Nobel Prize in 2012 and is currently under research in myriad fields, including Parkinson's disease.

"You can change the fate of cells by incorporating into them some new genes," said Dr Axel Behren, an expert in stem cell research from the Francis Crick Institute in London, who was not involved in the Ohio research. "Basically you can take a skin cell and put some genes into them, and they become another cell, for example a neuron, or a vascular cell, or a stem cell."

But the new approach, says Sen, avoids an intermediary step where cells are turned into what are known as pluripotent stem cells, instead turning skin cells directly into functional cells of different types. "It is a single step process in the body," he said.

Furthermore, the new approach does not rely on applying an electric field across a large area of the cell, or the use of viruses to deliver the genes. "We are the first to be able to reprogram [cells] in the body without the use of any viral vector," said Sen.

The new research, published in the journal Nature Nanotechnology, describes how the team developed both the new technique and novel genes, allowing them to reprogramme skin cells on the surface of an animal in situ.

"They can put this little device on one piece of skin or onto the other piece of skin and the genes will go there, wherever they put [the device]," said Behrens.

The team reveal that they used the technique on mice with legs that had had their arteries cut, preventing blood flow through the limb. The device was then put on the skin of the mice, and an electric field applied to trigger changes in the cells' membrane, allowing the genes to enter the cells below. As a result, the team found that they were able to convert skin cells directly into vascular cells -with the effect extending deeper into the limb, in effect building a new network of blood vessels.

"Seven days later we saw new vessels and 14 days later we saw [blood flow] through the whole leg," said Sen.

The team were also able to use the device to convert skin cells on mice, into nerve cells which were then injected into the brains of mice who had experienced a stroke, helping them to recover.

"With this technology, we can convert skin cells into elements of any organ with just one touch. This process only takes less than a second and is non-invasive, and then you're off," said Sen.

The new technology, said Behrens is an interesting step, not least since it "avoids all issues with rejection".

"This is a clever use of an existing technique that has potential applications -- but massive further refinement is needed," he said, pointing out that there are standard surgical techniques to deal with blockages of blood flow in limbs.

What's more, he said, the new technique is unlikely to be used on areas other than skin, since the need for an electric current and the device near to the tissue means using it on internal organs would require an invasive procedure.

"Massive development [would be] needed for this to be used for anything else than skin," he said.

But Sen and colleagues say they are hoping to develop the technique further, with plans to start clinical trials in humans next year.

2017 Guardian Web under contract with NewsEdge/Acquire Media. All rights reserved.

Image credit: The Ohio State University Wexner Medical Center.

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Nanochip Could Heal Injuries or Regrow Organs with One Touch - NewsFactor Network

Keeping a check on how many calories we consume helps to keep us looking trim from the outside. New research by collaborating scientists in the U.S. and Spain suggests that restricting calorie intake can also help to keep us more youthful on the inside by preventing age-related changes in how the natural rhythmical biological clocks within our cells work to control essential functions.

The two sets of studies in mice, by the team of Paolo Sassone-Corsi, Ph.D., at the University of California, Irvine (UCI), and by a research group headed by Salvador Aznar Benitah, Ph.D., at the Barcelona Institute of Science and Technology, have found that a low-calorie diet prevents age-related changes in the normal daily rhythmic oscillations in liver cell metabolism and adult stem cell functioning. They report their work in separate papers in the journal Cell that are entitled, Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging and Aged Stem Cells Reprogram Their Daily Rhythmic Functions to Adapt to Stress.

Its already known that the process of aging and circadian rhythms are linked, while restricting calorie intake in fruit flies extends the insects lifespan. Work by the UCI and Barcelona Institute of Science and Technology researchers has now demonstrated that calorie restriction (CR) can influence the interplay between circadian rhythms and aging processes in cells.

The liver operates at the interface between nutrition and energy distribution in the body, and metabolism is controlled within cells under circadian control, explains the UCI team, led by Dr. Sassone-Corsi, director of the Center for Epigenetics & Metabolism. To investigate the effects of aging on circadian control of metabolism at the cellular level, the team first looked at the effects of aging on rhythmic function and circadian gene expression in the liver cells of both young mice (aged 6 months) and older mice (aged 18 months) that were an unrestricted diet. They found that although both young and old mice demonstrated a circadian-controlled metabolic system, the mechanisms that control gene expression according to the cells usage of energy was altered in the old mice. In effect, their liver cells processed energy less efficiently.

However, when these older mice were fed a diet with 30% fewer calories for six months, the biological clock was reset, and circadian functions were restored to those of younger mice. caloric restriction works by rejuvenating the biological clock in a most powerful way, Sassone-Corsi said in a statement. In this context, a good clock meant good aging.

For the companion study, the Barcelona Institute of Science and Technology team worked with professor Sassone-Corsis team and with colleagues at the Catalan Institution for Research and Advanced Studies, the Universitat Pompeu Fabra, and the Spanish National Center for Cardiovascular Research to compare circadian rhythm functionality in skin stem cells in both young and old mice. Again, stem cells in older mice did retain a circadian rhythm, but exhibited significant reprogramming away from the expression of genes involved in homeostasis to those involved with tissue-specific stresses, such as DNA damage. The stem cells were effectively rewired to match tissue-specific age-related traits.This age-related rewiring of circadian functionality was again prevented by long-term CR in older mice.

The low-calorie diet greatly contributes to preventing the effects of physiological aging," commented Benitah. "Keeping the rhythm of stem cells 'young' is important because in the end these cells serve to renew and preserve very pronounced daynight cycles in tissue. Eating less appears to prevent tissue aging and, therefore, prevent stem cells from reprogramming their circadian activities."

Future studies will be needed to identify which components are responsible for the aging-related rewiring of the daily fluctuating functions of stem cells and to find out whether they could be targeted therapeutically to maintain the proper timing of stem cell function during aging in humans, the Spanish team suggests in their published paper.

"These studies also present something like a molecular holy grail, revealing the cellular pathway through which aging is controlled," Sassone-Corsi added. "The findings provide a clear introduction on how to go about controlling these elements of aging in a pharmacological perspective."

See the article here:
Calorie-Controlled Diet Restores Youthful Rhythmic Control of Metabolism in Old Mice - Genetic Engineering & Biotechnology News (blog)

The wonders of modern science know no bounds. Scientists in the U.S. have managedto grow brain cells from skin cells. They are now using tissue nanotransfection also known as TNT to grow brain cells on human skin. As a result, the skin can perform different functions, including boosting onescognitive abilities.

The human skin is not something most people think about too often, despite it being thebodys largest organ. We know it keeps our other organs inside of our body and protects us from cold, heat, and other weather conditions. It can also grow hair all over and even more in certain places to give us better protection against external threats. However, what it does under the hood is a major mystery to most people walking around on the surface of this planet. That may change pretty quickly thanks to a procedurecalledtissue nanotransfection.

Scientists have been enamored with this conceptfor some time now. Being able to make the human skin perform varioustasks based on evolvingneeds would unlock seemingly limitless possibility. The concept of using a microchip to grow brain cells on ones skin may not sound all thatappealing, but it should not be dismissed out of hand either. It is this chip which could make your skin perform all sorts of different functions, including improving your cognitive capabilities for a brief period of time.

Implanting chips within the human body is still a controversial idea. That stigma will remain present for quite some time, but developments such as tissue nanotransfection may help change things for the better. Harnessing this power through embedded microchips will allow humans to grow whatever type of cells they need at any given time. It can be used to speed up recovery from injury, fight off diseases, or even improve your brain capacity. That lastone sounds a bit scary, but it couldcertainly have its benefits.

The nanochip in question wasdeveloped by researchers at the Ohio State University Wexner Medical Center. This chip uses a small electric current to deliver DNA toliving skin cells, and effectively reprogramming them. Touch the chip to a wounded area, for example, and remove it immediately afterwards: the affected cells will start to heal faster and ensure the patient can recover more quickly. It will be interesting to see how human hosts respond to such treatment.

According to Nature Nanotechnology, this technique has been tested successfully onboth pigs and mice. Introducing new blood vessels to badly injured limbs savedthem fromlosing said limbs dueto lackluster blood flow. Additionally, the same technology has been used to create nerve cells from skin which canthen be harvested and injected into animals with brain injuries to help them recover. It shows a lot of potential for the future.

This new method ensures that immune suppression is no longer a necessity for the cells in question. It also bypassesthe conversion from skin to stem cell by transformingdirectly into whichever cell is needed at any given time. This is a very big leapand may ultimatelyalter the way we think abouthealth care altogether. The goal now is to successfully test the system usinghuman hosts and see how things play out in the long run.

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Scientists Develop Nanochip That Turns Skin Into Brain Cells - The Merkle

With a jolt from a tiny chip, humdrum skin cells may transform into medical mavericks.

A small electrical pulse blasts open tiny pores in cells and zaps in fragments of DNA or RNA loaded in the chips nanochannels. Those genetic deliveries then effectively reprogram the skin cells to act like other types of cells and repair damaged tissue. In early experiments on mice, researchers coaxed skin cells to act like brain cells. They also restored blood flow to a rodents injured limb by prompting skin cells to grow into new blood vessels.

The technology, published this week in Nature Nanotechnology, is still a long way from confirmed clinical applications in humans. But, the Ohio State researchers behind the chip are optimistic that it may one day perform myriad medical featsincluding healing severe injuries, restoring diseased organs, erasing brain damage, and even turning back the clock on aging tissues.

The researchers, led by regenerative medicine expert Chandan Sen and biomolecular engineer L. James Lee, expect to begin clinical trials next year.

The concept is very simple, Lee said in a press statement. As a matter of fact, we were even surprised how it worked so well. In my lab, we have ongoing research trying to understand the mechanism and do even better. So, this is the beginning, more to come.

Their concept is similar to other cell-based regenerative therapies under development, but it skips some pesky steps. Some other methods explored by researchersand dubious clinicsinvolve harvesting adult cells from patients, reprograming them to revert to stem cells, then injecting those cells back into patients, where they develop into a needed cell type.

But this setup has snags. Researchers often use viruses to deliver the genetic elements that reprogram the cells, which have caused cancer in some animal studies. The method also requires a lot of manipulation of cells in lab, adding complications. Its unclear if the suspect stem cell clinics are even successful at reprogramming cells.

The method used by Lee, Sen, and colleagues ditches the need for a virus and for any cellular handling. The electrical pulse opens pores in cells that allow for direct genetic deliverya process called electroporation. The researchers skipped the need to make stem cells by using preexisting methods of converting one cell type directly into a different one. Generally, this works by introducing bits of genetic material that code for gene regulators key to a specific cell type. Once delivered, these regulators can switch genes on or off so cells can start acting like the different cell type. Such a method has been worked out for creatingliver, brain, and vascular cellsfrom other cell types.

Finally, the researchers method also all takes place on a patch of skin on a living subject, potentially directly where its neededno cell harvesting or lab manipulations are required. (That said, the researchers note that future therapies could use skin patches to generate specific cell types that can then be transferred to other locations in the body if needed.)

So far, the researchers have dabbled with making brain cells and vasculature cells from skin cells. In early experiments, their direct delivery proved effective at converting the cells. The researcher verified that the converted cells mirrored normal brain and vasculature cells' gene expression profilesthe pattern of genes they have turned on and off.

In their ultimate test, the researchers severed leg arteries in ahandful of mice. Then a researcher placed over the injuries nanochips loaded with genetic ingredients for converting skin cells to vasculature cells. The conversion reached cells deep within the skin layers. After a week, the researchers saw more blood flow and less tissue death in the treated mice compared withcontrol animals that werent treated.

Much work still needs to be done to test the idea and prove it's effective for certain treatments. But the researchers are optimistic. They conclude in the study that the technology has the potential to ultimately enable the use of a patients own tissue as a prolific immunosurveilled bioreactor.

Nature Nanotechnology, 2017. DOI: 10.1038/nnano.2017.134 (About DOIs).

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Heal thyself: Skin-zapping chip aims to reprogram cells for tissue repair - Ars Technica

Skin transplantation could be an effective way to deliver gene therapy to treat type 2 diabetes and obesity, new research in mice suggests.

The technique could enable a wide range of gene-based therapies to treat many human diseases.

We think this can provide a long-term safe option for the treatment of many diseases

We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems, says study author Xiaoyang Wu, assistant professor in the cancer research department at the University of Chicago.

We think this platform has the potential to lead to safe and durable gene therapy in mice and, we hope, in humans, using selected and modified cells from skin.

Beginning in the 1970s, physicians learned how to harvest skin stem cells from a patient with extensive burn wounds, grow them in the laboratory, then apply the lab-grown tissue to close and protect a patients wounds. This approach is now standard. However, the application of skin transplants is better developed in humans than in mice.

The mouse system is less mature, Wu says. It took us a few years to optimize our 3D skin organoid culture system.

This study is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems.

We have a better than 80 percent success rate with skin transplantation, Wu says. This is exciting for us.

The researchers focused on diabetes because it is a common non-skin disease that can be treated by the strategic delivery of specific proteins.

They inserted the gene for glucagon-like peptide 1 (GLP1), a hormone that stimulates the pancreas to secrete insulin. This extra insulin removes excessive glucose from the bloodstream, preventing the complications of diabetes. GLP1 can also delay gastric emptying and reduce appetite.

Using CRISPR, a tool for precise genetic engineering, they modified the GLP1 gene. They inserted one mutation, designed to extend the hormones half-life in the blood stream, and fused the modified gene to an antibody fragment so that it would circulate in the blood stream longer. They also attached an inducible promoter, which enabled them to turn on the gene to make more GLP1, as needed, by exposing it to the antibiotic doxycycline. Then they inserted the gene into skin cells and grew those cells in culture.

When these cultured cells were exposed to an air/liquid interface in the laboratory, they stratified, generating what the authors referred to as a multi-layered, skin-like organoid.

Next, they grafted this lab-grown gene-altered skin onto mice with intact immune systems. There was no significant rejection of the transplanted skin grafts.

When the mice ate food containing minute amounts of doxycycline, they released dose-dependent levels of GLP1 into the blood. This promptly increased blood-insulin levels and reduced blood-glucose levels.

When the researchers fed normal or gene-altered mice a high-fat diet, both groups rapidly gained weight. They became obese. When normal and gene-altered mice got the high-fat diet along with varying levels of doxycycline, to induce GLP1 release, the normal mice grew fat and mice expressing GLP1 showed less weight gain.

Expression of GLP1 also lowered glucose levels and reduced insulin resistance.

Together, our data strongly suggest that cutaneous gene therapy with inducible expression of GLP1 can be used for the treatment and prevention of diet-induced obesity and pathologies, the authors write.

When they transplanted gene-altered human cells to mice with a limited immune system, they saw the same effect. These results, the authors wrote, suggest that cutaneous gene therapy for GLP1 secretion could be practical and clinically relevant.

This approach, combining precise genome editing in vitro with effective application of engineered cells in vivo, could provide significant benefits for the treatment of many human diseases, the authors note.

We think this can provide a long-term safe option for the treatment of many diseases, Wu says. It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect, such as hemophilia. Or it could function as a metabolic sink, removing various toxins.

Skin progenitor cells have several unique advantages that are a perfect fit for gene therapy. Human skin is the largest and most accessible organ in the body. It is easy to monitor. Transplanted skin can be quickly removed if necessary. Skins cells rapidly proliferate in culture and can be easily transplanted. The procedure is safe, minimally invasive, and inexpensive.

There is also a need. More than 100 million US adults have either diabetes (30.3 million) or prediabetes (84.1 million), according the Centers for Disease Control and Prevention. More than two out of three adults are overweight. More than one out of three are considered obese.

Additional authors of the study are from the University of Chicago and the University of Illinois at Chicago. The National Institutes of Health, the American Cancer Society, and the V Foundation funded the study.

Source: University of Chicago

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Skin transplants could treat diabetes and obesity - Futurity - Futurity: Research News

Technologies that reprogram one type of cell to perform the role of another hold a huge amount of potential when it comes to medicine, possibly changing the way we treat everything from Parkinson's to pancreatic cancer to brain tumors. One broader outcome of all of this could be a game-changing ability to repair and restore damaged tissue and organs. Scientists are now reporting a promising advance in the area, in the form of patch that they say can use an electric pulse to turn skin cells into the building blocks of any organ.

The new technology has been dubbed tissue nanotransfection and was developed by scientists at The Ohio State University's Wexner Medical Center. According to the researchers, it uses the skin as a kind of regenerative cellular factory, where it produces any cell type that can then be used to repair injured or aging tissues, organs and blood vessels. It consists of a nanotechnology-based chip that is applied to the skin, which is then struck with a short electric pulse to deliver genetic instructions into the cells of the tissue.

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"These are genes that induce tissue plasticity allowing the flexibility to direct the fate," Chandan Sen, first author of the paper, explains to New Atlas. "Thus, for example, skin cells can be directed to form blood vessels, or neural cells, or some other cell of interest."

We have seen a number of promising approaches to reprogramming cells for various regenerative health purposes. In 2012, a Japanese researcher won a Nobel Prize for his discovery that skin cells from mice could be harvested and converted into stem cells in the lab, work that has inspired a number of exciting breakthroughs since.

But according to Sen, one of the main advantages his tissue nanotransfection technology holds over other approaches is the fact that the cell conversion takes place in the body. This avoids the thorny issue of immune response, in which the host cells react to the newcomers and possibly attack them, something that can cause a raft of complications.

"Ours is reprogramming of not just cells but tissue within the live body under immune surveillance," he tells us. "Our strategy must co-operate with physiological factors to achieve the end goal."

That end goal is still a while away, but his team is making promising progress all the same. It put the technology to the test on animals, and in one experiment involving mice with badly injured legs lacking blood flow, it was able to convert skin cells into vascular cells. Within about a week, the legs featured active blood vessels. By the second week they were saved.

In a separate experiment, the team was also able to use the technology to reprogram skin cells into nerve cells, which were then injected into brain-injured mice to assist with stroke recovery.

"This is difficult to imagine, but it is achievable, successfully working about 98 percent of the time," said Sen. "With this technology, we can convert skin cells into elements of any organ with just one touch. This process only takes less than a second and is non-invasive, and then you're off. The chip does not stay with you, and the reprogramming of the cell starts. Our technology keeps the cells in the body under immune surveillance, so immune suppression is not necessary."

The team hopes to move onto clinical trials some time next year, but Sen tells us they must first test the technology on larger animals and design the device to work on humans.

You can hear from Sen in the video below, while the research was published in the journal Nature Nanotechnology.

Source: Ohio State University

The rest is here:
Chip reprograms skin cells with a short electric pulse - New Atlas - New Atlas

A University of Chicago-based research team has overcome challenges that have limited gene therapy and demonstrated how their novel approach with skin transplantation could enable a wide range of gene-based therapies to treat many human diseases.

In a study inthe journal Cell Stem Cell, the researchers provide proof-of-concept. They describe gene-therapy administered through skin transplants to treat two related and extremely common human ailments: Type 2 diabetes and obesity.

We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems, said study author Xiaoyang Wu, assistant professor in the Ben May Department for Cancer Research at the University of Chicago. We think this platform has the potential to lead to safe and durable gene therapy in mice and, we hope, in humans, using selected and modified cells from skin.

Beginning in the 1970s, physicians learned how to harvest skin stem cells from a patient with extensive burn wounds, grow them in the laboratory, then apply the lab-grown tissue to close and protect a patients wounds. This approach is now standard. However, the application of skin transplants is better developed in humans than in mice.

The mouse system is less mature, Wu said. It took us a few years to optimize our 3-D skin organoid culture system.

This study is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems. We have a better than 80 percent success rate with skin transplantation, Wu said. This is exciting for us.

The researchers focused on diabetes because it is a common non-skin disease that can be treated by the strategic delivery of specific proteins.

They inserted the gene for glucagon-like peptide 1 (GLP1), a hormone that stimulates the pancreas to secrete insulin. This extra insulin removes excessive glucose from the bloodstream, preventing the complications of diabetes. GLP1 can also delay gastric emptying and reduce appetite.

Using CRISPR, a tool for precise genetic engineering, they modified the GLP1 gene. They inserted one mutation, designed to extend the hormones half-life in the blood stream, and fused the modified gene to an antibody fragment so that it would circulate in the blood stream longer. They also attached an inducible promoter, which enabled them to turn on the gene to make more GLP1, as needed, by exposing it to the antibiotic doxycycline. Then they inserted the gene into skin cells and grew those cells in culture.

When these cultured cells were exposed to an air/liquid interface in the laboratory, they stratified, generating what the authors referred to as a multi-layered, skin-like organoid. Next, they grafted this lab-grown gene-altered skin onto mice with intact immune systems. There was no significant rejection of the transplanted skin grafts.

When the mice ate food containing minute amounts of doxycycline, they released dose-dependent levels of GLP1 into the blood. This promptly increased blood-insulin levels and reduced blood-glucose levels.

When the researchers fed normal or gene-altered mice a high-fat diet, both groups rapidly gained weight. They became obese. When normal and gene-altered mice got the high-fat diet along with varying levels of doxycycline, to induce GLP1 release, the normal mice grew fat and mice expressing GLP1 showed less weight gain.

Expression of GLP1 also lowered glucose levels and reduced insulin resistance.

Together, our data strongly suggest that cutaneous gene therapy with inducible expression of GLP1 can be used for the treatment and prevention of diet-induced obesity and pathologies, the authors wrote.

When they transplanted gene-altered human cells to mice with a limited immune system, they saw the same effect. These results, the authors wrote, suggest that cutaneous gene therapy for GLP1 secretion could be practical and clinically relevant.

This approach, combining precise genome editing in vitro with effective application of engineered cells in vivo, could provide significant benefits for the treatment of many human diseases, the authors note.

We think this can provide a long-term safe option for the treatment of many diseases, Wu said. It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect, such as hemophilia. Or it could function as a metabolic sink, removing various toxins.

Skin progenitor cells have several unique advantages that are a perfect fit for gene therapy. Human skin is the largest and most accessible organ in the body. It is easy to monitor. Transplanted skin can be quickly removed if necessary. Skins cells rapidly proliferate in culture and can be easily transplanted. The procedure is safe, minimally invasive and inexpensive.

There is also a need. More than 100 million U.S. adults have either diabetes (30.3 million) or prediabetes (84.1 million), according the Centers for Disease Control and Prevention. More than two out of three adults are overweight. More than one out of three are considered obese.

Additional authors of the study were Japing Yue, Queen Gou, and Cynthia Li from the University of Chicago and Barton Wicksteed from the University of Illinois at Chicago. The National Institutes of Health, the American Cancer Society and the V Foundation funded the study.

Article originally appeared on Science Life.

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Gene therapy via skin could treat diseases such as obesity - UChicago News

Theoretically, eternal youth is now within our grasp.

Doctors are close to discovering a real life fountain of youth that could theoretically enable patients to live forever. Advances in stem cell treatments and now, tissue nanotransfection (TNT), which is a new technique, can theoretically provide patients with the benefits of youth for life.

The fountain of youth is within the grasp of science, but so far, only for mice. Human trials come next year.

LOS ANGELES, CA (California Network) -- The quest for eternal life is ancient. It is mentioned in the first and oldest story we have, the Epic of Gilgamesh. In that ancient Sumerian tale, only Utnapishtim, a man who built and ark and survived a great flood in a story that is almost identical to the story of Noah's ark, knows the secret to eternal life, which ultimately proves elusive. In the centuries that followed, people have tried every remedy imaginable to prolong life. They searched for the fabled fountain of youth, and according to some legends, bathed in the blood of virgins and children.

Today, we know none of these endeavors would work because ageing is carried on in the genes. The only way to reverse ageing is to manipulate the genes. And this is precisely what doctors are looking to do in order to produce new cells, and even whole organs.

Researchers now know the primary difference between a young person and an old person is the number of stem cells in their body. Young people have many times more stem cells. This is the basic, underlying reason why young people are so youthful. A young body can repair itself more rapidly and thoroughly than an older one because of the number of stem cells. But if stem cells could be injected into an older body, in quantities similar to those enjoyed by a young person, what would happen then?

Nobody knows for certain because the experiment hasn't been conducted, but the hypothesis is that the older person would become more youthful, healthier, and longer lived.

As stem cells enter the medical mainstream, and may become a standard part of medical treatment in the near future, there is another development that could make stem cells irrelevant. Nanotransfection, abbreviated as TNT, is a new method whereby skin cells can be turned into any other cell in the body using a special microchip and electricity.

The device, called a nanochip, is loaded with genetic material essential to turning cells into other kinds of cells. The electrical current enables the device to inject the genetic material into the skin where it ends up inside the cells. These cells can then travel though the body and take on the properties of healthy cells around damaged tissue, facilitating repair. On other words, a damaged liver or heart can be repaired with this tiny device. The advantage of this method is that stem cells are not required. Your skin cells simply become whether other kind of cells they are told to become by the injected genetic material.

A study affirming the effectiveness of this approach was published in the journal, Nature Nanotechnology. It has been tested on mice and was successful in restoring function to non-functioning limbs. It will be tested on humans within the next year.

Scientists have known they can reprogram cells into other kinds of cells for a long time now, but only recently have they developed the method to do so cheaply and efficiently. The actual procedure requires a chip that is as small as a penny, and takes only a second to work.

If the procedure works on humans, then doctors may have a cheap and efficient way to repair and even replace organs. The discovery is so dramatic is it difficult to believe. More testing is required, but it shows just how far we have come in our ability to edit genes and reprogram cells to grow specific forms of tissue within the body.

In a generation or less, it is reasonable that we will have unlocked the secret to reversing ageing. Of course, this discovery opens a whole host of ethical and philosophical questions, but that's for the ethicists and politicians to work out. For now, science is about to take the first sip from the fountain of youth, and we await the result.

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Pope Francis Prayer Intentions for JULY 2017Lapsed Christians. That our brothers and sisters who have strayed from the faith, through our prayer and witness to the Gospel, may rediscover the merciful closeness of the Lord and the beauty of the Christian life.

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Stem cells: science prepares to take the first sip from the real fountain of youth - Catholic Online

A med-tech startup has developed a fast and easy way to treat certain burn wounds with stem cells. This technology is developed by German researcher Dr. Jrg Gerlach. He is the worlds first ever person who use a patients stem cells to directly heal the skin. The technique is meant to reduce the healing time and minimize complications, with aesthetically and functionally satisfying outcomes. There are no scars, no residual pain and its like there wasnt any burn to start with. Its not less than a miracle.

The medical technology startup has now transformed the proof-of-concept device from a complicated prototype into a user-friendly product called a SkinGun, which it hopes doctors will be able to use outside of an experimental setting. RenovaCare CEO Thomas Bold believes, the SkinGun can compete with, or even replace, todays standard of care. The sprayer allows us to have a generous distribution of cells on the wound, explained Roger Esteban-Vives, director of cell sciences at RenovaCare.

RenovaCares SkinGun sprays a liquid suspension of a patients stem cells onto a burn or wound in order to re-grow the skin without scars. Stem-cell methods helped cut this risk by quickening healing and providing a source of new skin from a very small area. Cell Mist method gets a greater yield from its harvest than mesh grafting, a more common way to treat burns. At a maximum, grafting can treat six times the size of its harvest area. Cell Mist can cover 100 times its harvest area.

When dispensing cells over a wound, its important that they make the transition without any damage. Damaged cells reduce the effectiveness of the treatment.

High cell viability also contributes to faster healing. When a wound heals naturally, cells migrate to it to build up the skin. That process can take weeks.

Stem cells have tremendous promise to help us understand and treat a range of diseases, injuries and other health-related conditions.

There is still a lot to learn about stem cells, however, and their current applications as treatments are sometimes exaggerated by the media and other parties who do not fully understand the science and current limitations

Beyond regulatory matters, there are also limitations to the technology that make it unsuitable for competing with treatments of third-degree burns, which involve damage to muscle and other tissue below the skin.

When burn victims need a skin graft they typically have to grow skin on other parts of their bodies. This is a process that can take weeks. A new technique uses stem cells derived from the umbilical cord to generate new skin much more quickly.The umbilical cord consists of a gelatinous tissue that contains uncommitted mesenchymal stemcells (MSC)

Research is underway to develop various sources for stem cells, and to apply stem-cell treatments for neurodegenertive diseasesand conditions such as diabetes, heart disease, and other conditions.

Tens of thousands of grafts are performed each year for burn victims, cosmetic surgery patients, and for people with large wounds having difficulty healing. Traditionally, this involves taking a large patch of skin (typically from the thigh) and removing the dermis and epidermis to transplant elsewhere on the body. Burns victims are making incredible recoveries thanks to a revolutionary gun that sprays stem cells on to their wounds, enabling them to rapidly grow new skin. Patients who have benefited say their new skin is virtually indistinguishable from that on the rest of the body.

Thomas Bold, chief executive of RenovaCare, the company behind SkinGun, said: The procedure is gentler and the skin that regrows looks, feels and functions like the original skin.

If you are planning to have stem cell treatments dont forget to remember these points

Stem cell researchers are making great advances in understanding normal development. They are trying to figure out what goes wrong in disease and developing and testing potential treatments to help patients. They still have much to learn. However, about how stem cells work in the body and their capacity for healing. Safe and effective treatments for most diseases, conditions and injuries are in the future.

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Dramatic Burn-Healing Through Stem Cell Treatment - Fox Weekly

Researchers demonstrate a process known as tissue nanotransfection (TNT). When it comes to healing, this TNT is the bomb.

It's usually bad news to have something growing on your skin, but new technology uses that all important layer as a sort of garden to "grow" whatever types of cells your body might need to treat an injury or disease, be it in a limb or even the brain.

Researchers atthe Ohio State University Wexner Medical Centerhave developed a nanochip that uses a small electrical current to deliver new DNA or RNA into living skin cells, "reprogramming" them and giving them a new function.

"It takes just a fraction of a second. You simply touch the chip to the wounded area, then remove it,"Chandan Sen, director of the Center for Regenerative Medicine and Cell-Based Therapies at Ohio State, said in a statement. "At that point, the cell reprogramming begins."

In a study published in the journal Nature Nanotechnology, Sen's team used a technology called Tissue Nanotransfection (TNT) to create new blood vessels in pigs and mice with badly injured limbs that lacked blood flow.

They zapped the animals' skin with the device, and within about a week, active blood vessels appeared, essentially saving the creatures' legs. The tech was also used to create nerve cells from skin that were then harvested and injected into mice with brain injuries to help them recover.

"By using our novel nanochip technology, injured or compromised organs can be replaced," Sen said. "We have shown that skin is a fertile land where we can grow the elements of any organ that is declining."

While it sounds futuristic, reprogramming skin cells is not a new idea. The ability to change skin into pluripotent stem cells, sometimes called "master" cells, earned a few scientists a Nobel Prize half a decade ago. But the new nanochip approach improves upon that discovery by skipping the conversion from skin to stem cell and instead converting a skin cell into whatever type of cell is desired in a single step.

"Our technology keeps the cells in the body under immune surveillance, so immune suppression is not necessary," Sen says.

By now I think we've all learned that beauty is only skin deep, but it might take a while to learn that the same could go for cures, at least if the system works just as well on people.

Next up, the scientists hope to find out by continuing to test their technology in human trials. The aim is that it could eventually be used to treat all sorts of organ and tissue failure, including diseases like Parkinson's and Alzheimers.

Crowd Control: A crowdsourced science fiction novel written by CNET readers.

Solving for XX:The tech industry seeks to overcome outdated ideas about "women in tech."

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Wild new microchip tech could grow brain cells on your skin - CNET

The chip has not been tested in humans, but it has been used to heal wounds in mice. Wexner Medical Center/The Ohio State University hide caption

The chip has not been tested in humans, but it has been used to heal wounds in mice.

Scientists have created an electronic wafer that reprogrammed damaged skin cells on a mouse's leg to grow new blood vessels and help a wound heal.

One day, creator Chandan Sen hopes, it could be used to be used to treat wounds on humans. But that day is a long way off as are many other regeneration technologies in the works. Like Sen, some scientists have begun trying to directly reprogram one cell type into another for healing, while others are attempting to build organs or tissues from stem cells and organ-shaped scaffolding.

But other scientists have greeted Sen's mouse experiment, published in Nature Nanotechnology on Monday, with extreme skepticism. "My impression is that there's a lot of hyperbole here," says Sean Morrison, a stem cell researcher at the University of Texas Southwestern Medical Center. "The idea you can [reprogram] a limited number of cells in the skin and improve blood flow to an entire limb I think it's a pretty fantastic claim. I find it hard to believe."

When the device is placed on live skin and activated, it sends a small electrical pulse onto the skin cells' membrane, which opens a tiny window on the cell surface. "It's about 2 percent of the cell membrane," says Sen, who is a researcher in regenerative medicine at Ohio State University. Then, using a microscopic chute, the chip shoots new genetic code through that window and into the cell where it can begin reprogramming the cell for a new fate.

Sen says the whole process takes less than 0.1 seconds and can reprogram the cells resting underneath the device, which is about the size of a big toenail. The best part is that it's able to successfully deliver its genetic payload almost 100 percent of the time, he says. "No other gene delivery technique can deliver over 98 percent efficiency. That is our triumph."

Chandan Sen, a researcher at Ohio State University, holds a chip his lab created that has reprogrammed cells in mice. Wexner Medical Center/The Ohio State University hide caption

Chandan Sen, a researcher at Ohio State University, holds a chip his lab created that has reprogrammed cells in mice.

To test the device's healing capabilities, Sen and his colleagues took a few mice with damaged leg arteries and placed the chip on the skin near the damaged artery. That reprogrammed a centimeter or two of skin to turn into blood vessel cells. Sen says the cells that received the reprogramming genes actually started replicating the reprogramming code that the researchers originally inserted in the chip, repackaging it and sending it out to other nearby cells. And that initiated the growth of a new network of blood vessels in the leg that replaced the function of the original, damaged artery, the researchers say. "Not only did we make new cells, but those cells reorganized to make functional blood vessels that plumb with the existing vasculature and carry blood," Sen says. That was enough for the leg to fully recover. Injured mice that didn't get the chip never healed.

When the researchers used the chip on healthy legs, no new blood vessels formed. Sen says because injured mouse legs were was able to incorporate the chip's reprogramming code into the ongoing attempt to heal.

That idea hasn't quite been accepted by other researchers, however. "It's just a hand waving argument," Morrison says. "It could be true, but there's no evidence that reprogramming works differently in an injured tissue versus a non-injured tissue."

What's more, the role of exosomes, the vesicles that supposedly transmit the reprogramming command to other cells, has been contentious in medical science. "There are all manners of claims of these vesicles. It's not clear what these things are, and if it's a real biological process or if it's debris," Morrison says. "In my lab, we would want to do a lot more characterization of these exosomes before we make any claims like this."

Sen says that the theory that introduced reprogramming code from the chip or any other gene delivery method does need more work, but he isn't deterred by the criticism. "This clearly is a new conceptual development, and skepticism is understandable," he says. But he is steadfast in his confidence about the role of reprogrammed exosomes. When the researchers extracted the vesicles and injected them into skin cells in the lab, Sen says those cells converted into blood vessel cells in the petri dish. "I believe this is definitive evidence supporting that [these exosomes] may induce cell conversion."

Even if the device works as well as Sen and his colleagues hope it does, they only tested it on mice. Repairing deeper injuries, like vital organ damage, would also require inserting the chip into the body to reach the wound site. It has a long way to go before it can ever be considered for use on humans. Right now, scientists can only directly reprogram adult cells into a limited selection of other cell types like muscle, neurons and blood vessel cells. It'll be many years before scientists understand how to reprogram one cell type to become part of any of our other, many tissues.

Still, Morrison says the chip is an interesting bit of technology. "It's a cool idea, being able to release [genetic code] through nano channels," he says. "There may be applications where that's advantageous in some way in the future."

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A Chip That Reprograms Cells Helps Healing, At Least In Mice - NPR

The PASE, or post-implantation amniotic sac embryoid, is a structure grown from human pluripotent stem cells that mimics many of the properties of the amniotic sac that forms soon after an embryo implants in the uterus wall. The structures could be used to study infertility. Credit: University of Michigan

The first few weeks after sperm meets egg still hold many mysteries. Among them: what causes the process to fail, leading to many cases of infertility.

Despite the importance of this critical stage, scientists haven't had a good way to explore what can go wrong, or even what must go right, after the newly formed ball of cells implants in the wall of the human uterus.

But a new achievement using human stem cells may help change that. Tiny lab-grown structures could give researchers a chance to see what they couldn't before, while avoiding ethical issues associated with studying actual embryos.

A team from the University of Michigan reports in Nature Communications that they have coaxed pluripotent human stem cells to grow on a specially engineered surface into structures that resemble an early aspect of human development called the amniotic sac.

The cells spontaneously developed some of the same structural and molecular features seen in a natural amniotic sac, which is an asymmetric, hollow ball-like structure containing cells that will give rise to a part of the placenta as well as the embryo itself. But the structures grown at U-M lack other key components of the early embryo, so they can't develop into a fetus.

It's the first time a team has grown such a structure starting with stem cells, rather than coaxing a donated embryo to grow, as a few other teams have done.

"As many as half of all pregnancies end in the first two weeks after fertilization, often before the woman is even aware she is pregnant. For some couples, there is a chronic inability to get past these critical early developmental steps, but we have not previously had a model that would allow us to explore the reasons why," says co-senior author Deborah Gumucio, Ph.D. "We hope this work will make it possible for many scientists to dig deeper into the pathways involved in normal and abnormal development, so we can understand some of the most fascinating biology on earth." Gumucio is the Engel Collegiate Professor of Cell & Developmental Biology at Michigan Medicine, U-M's academic medical center.

A steady PASE

The researchers have dubbed the new structure a post-implantation amniotic sac embryoid, or PASE. They describe how a PASE develops as a hollow spherical structure with two distinct halves that remain stable even as cells divide.

One half is made of cells that will become amniotic ectoderm, the other half consists of pluripotent epiblast cells that in nature make up the embryonic disc. The hollow center resembles the amniotic cavity - which in normal development eventually gives rise to the fluid-filled sac that protects and cushions the fetus during development.

Gumucio likens a PASE to a mismatched plastic Easter egg or a blue-and-red Pokmon ball - with two clearly divided halves of two kinds of cells that maintain a stable form around a hollow center.

The team also reports details about the genes that became activated during the development of a PASE, and the signals that the cells in a PASE send to one another and to neighboring tissues. They show that a stable two-halved PASE structure relies on a signaling pathway called BMP-SMAD that's known to be critical to embryo development.

Gumucio notes that the PASE structures even exhibit the earliest signs of initiating a "primitive streak", although it did not fully develop. In a human embryo, the streak would start a process called gastrulation. That's the division of new cells into three cell layersendoderm, mesoderm and ectodermthat are essential to give rise to all organs and tissues in the body.

Collaboration provides the spark

The new study follows directly from previous collaborative work between Gumucio's lab and that of the other senior author, U-M mechanical engineering associate professor Jianping Fu, Ph.D.

In the previous work, reported in Nature Materials, the team succeeded in getting balls of stem cells to implant in a special surface engineered in Fu's lab to resemble a simplified uterine wall. They showed that once the cells attached themselves to this substrate, they began to differentiate into hollow cysts composed entirely of amnion - a tough extraembryonic tissue that holds the amniotic fluid.

But further analysis of these cysts by co-first authors of the new paper Yue Shao, Ph.D., a graduate student in Fu's lab, and Ken Taniguchi, a postdoctoral fellow in Gumucio's lab, revealed that a small subset of these cysts were stably asymmetric and looked exactly like early human or monkey amniotic sacs.

The team found that such structures could also grow from induced pluripotent stem cells (iPSCs)cells derived from human skin and grown in the lab under conditions that give them the ability to become any type of cell, similar to how embryonic stem cells behave. This opens the door for future work using skin cells donated by couples experiencing chronic infertility, which could be grown into iPSCs and tested for their ability to form proper amniotic sacs using the methods devised by the team.

Important notes and next steps

Besides working with genetic and infertility specialists to delve deeper into PASE biology as it relates to human infertility, the team is hoping to explore additional characteristics of amnion tissue.

For example, early rupture of the amnion tissue can endanger a fetus or be the cause of a miscarriage. The team also intends to study which aspects of human amnion formation also occur in development of mouse amnion. The mouse embryo model is very attractive as an in vivo model for investigating human genetic diseases.

The team's work is overseen by a panel that monitors all work done with pluripotent stem cells at U-M, and the studies are performed in accordance with laws regarding human stem cell research. The team ends experiments before the balls of cells effectively reach 14 developmental days, the cutoff used as an international limit on embryo researcheven though the work involves tissue that cannot form an embryo. Some of the stem cell lines were derived at U-M's privately funded MStem Cell Laboratory for human embryonic stem cells, and the U-M Pluripotent Stem Cell Core.

Explore further: Team uses stem cells to study earliest stages of amniotic sac formation

More information: Yue Shao et al, A pluripotent stem cell-based model for post-implantation human amniotic sac development, Nature Communications (2017). DOI: 10.1038/s41467-017-00236-w

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Amniotic sac in a dish: Stem cells form structures that may aid of ... - Phys.Org

The Potential of CRISPR

The potential of the gene editing toolCRISPRjust seems to keep growing and growing, and the latest experimental use of the technology is creating skin grafts that trigger the release of insulin and help manage diabetes.

Researchers have successfully tested the idea with mice that gained less weight and showed a reversed resistance to insulin because of the grafts (high insulin resistance is a common precursor to type 2 diabetes).

In fact, the team from the University of Chicago says the same approach could eventually be used to treat a variety of metabolic and genetic conditions, not just diabetes its a question of using skin cells to trigger different chemical reactions in the body.

We didnt cure diabetes, but it does provide a potential long-term and safe approach of using skin epidermal stem cells to help people with diabetes and obesity better maintain their glucose levels,says one of the researchers, Xiaoyang Wu.

If youre new to theCRISPR(Clustered Regularly Interspaced Short Palindromic Repeats) phenomenon, its a new and innovative way of editing specific genes in the body, using a biological copy and paste technique: it can doeverything fromcut out HIV virus DNA to slow thegrowth of cancer cells.

For this study, researchers used CRISPR to alter the gene responsible for encoding a hormone calledglucagon-like peptide-1(GLP-1), which triggers the release of insulin and then helps remove excess glucose from the blood.

Type 2 diabetescomes about due to a lack of insulin, also known as insulin resistance.

Using CRISPR, the GLP-1 gene could be tweaked to make its effects last longer than normal. The result was developed into skin grafts that were then applied to mice.

Around 80 percent of the grafts successfully released the edited hormone into the blood, regulating blood glucose levels over four months, as well as reversing insulin resistance and weight gain related to a high-fat diet.

Significantly, its the first time the skin graft approach has worked for mice not specially designed in the lab.

This paper is exciting for us because it is the first time we show engineered skin grafts can survive long term in wild-type mice, and we expect that in the near future this approach can be used as a safe option for the treatment of human patients,says Wu.

Human treatments will take time to develop but the good news is that scientists are today able to grow skin tissue very easily in the lab using stem cells, so that wont be an issue.

If we can make it safe, and patients are happy with the procedure, then the researchers say it could be extended to treat something likehaemophilia, where the body is unable to make blood clots properly.

Any kind of disease where the body is deficient in specific molecules could potentially be targeted by this new technique. And if it works with diabetes, it could be time to say goodbye to needles and insulin injections.

Other scientists who werent directly involved in the research, including Timothy Kieffer from the University of British Columbia in Canada, seem optimistic.

I do predict that gene and cell therapies will ultimately replace repeated injections for the treatment of chronic diseases, Kieffer told Rachel Baxter atNew Scientist.

The findings have been published inCell Stem Cell.

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CRISPR Skin Grafts Could Replace Insulin Shots For Diabetes - Futurism

A novel device that reprogrammes skin cells could represent a breakthrough in repairing injured or ageing tissue, researchers say.

The new technique, called tissue nanotransfection, is based on a tiny device that sits on the surface of the skin of a living body. An intense, focused electric field is then applied across the device, allowing it to deliver genes to the skin cells beneath it turning them into different types of cells.

That, according to the researchers, offers an exciting development when it comes to repairing damaged tissue, offering the possibility of turning a patients own tissue into a bioreactor to produce cells to either repair nearby tissues, or for use at another site.

By using our novel nanochip technology, injured or compromised organs can be replaced, said Chandan Sen, from the Ohio State University, who co-led the study. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining.

The ability for scientists to reprogram cells into other cell types is not new: the discovery scooped John Gurdon and Shinya Yamanaka the Nobel Prize in 2012 and is currently under research in myriad fields, including Parkinsons disease.

You can change the fate of cells by incorporating into them some new genes, said Dr Axel Behrens, an expert in stem cell research from the Francis Crick Institute in London, who was not involved in the Ohio research. Basically you can take a skin cell and put some genes into them, and they become another cell, for example a neuron, or a vascular cell, or a stem cell.

But the new approach, says Sen, avoids an intermediary step where cells are turned into what are known as pluripotent stem cells, instead turning skin cells directly into functional cells of different types. It is a single step process in the body, he said.

Furthermore, the new approach does not rely on applying an electric field across a large area of the cell, or the use of viruses to deliver the genes. We are the first to be able to reprogramme [cells] in the body without the use of any viral vector, said Sen.

The new research, published in the journal Nature Nanotechnology, describes how the team developed both the new technique and novel genes, allowing them to reprogramme skin cells on the surface of an animal in situ.

They can put this little device on one piece of skin or onto the other piece of skin and the genes will go there, wherever they put [the device], said Behrens.

The team reveal that they used the technique on mice with legs that had had their arteries cut, preventing blood flow through the limb. The device was then put on the skin of the mice, and an electric field applied to trigger changes in the cells membrane, allowing the genes to enter the cells below. As a result, the team found that they were able to convert skin cells directly into vascular cells -with the effect extending deeper into the limb, in effect building a new network of blood vessels.

Seven days later we saw new vessels and 14 days later we saw [blood flow] through the whole leg, said Sen.

The team were also able to use the device to convert skin cells on mice, into nerve cells which were then injected into the brains of mice who had experienced a stroke, helping them to recover.

With this technology, we can convert skin cells into elements of any organ with just one touch. This process only takes less than a second and is non-invasive, and then youre off, said Sen.

The new technology, said Behrens is an interesting step, not least since it avoids all issues with rejection.

This is a clever use of an existing technique that has potential applications but massive further refinement is needed, he said, pointing out that there are standard surgical techniques to deal with blockages of blood flow in limbs.

Whats more, he said, the new technique is unlikely to be used on areas other than skin, since the need for an electric current and the device near to the tissue means using it on internal organs would require an invasive procedure.

Massive development [would be] needed for this to be used for anything else than skin, he said.

But Sen and colleagues say they are are hoping to develop the technique further, with plans to start clinical trials in humans next year.

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Nanochip could heal injuries or regrow organs with one touch, say researchers - The Guardian

A proof-of-concept study in mice has demonstrated how skin grafts could deliver gene therapy for obesity and diabetes.

'We think this platform has the potential to lead to safe and durable gene therapy, in mice and we hope, someday, in humans, using selected and modified cells from skin,' said senior author Dr Xiaoyang Wu of the University of Chicago, Illinois.

The technique explores the potential of glucagon-like peptide 1 (GLP1), a hormone which could help to treat conditions like diabetes and obesity. GLP1 reduces appetite and stimulates the release of insulin to lowerblood sugar, butdoes not last long in the blood and is challenging to deliver orally.

The researchers used CRISPR to edit skin stem cellstaken from newborn mice. They inserted a modified version of the GLP1 gene, designed to increase the duration of the hormone, and a genetic'switch' to turn the gene on in the presence of an antibiotic.

They grew the skin stem cells into a skin organoids, and grafted them onto mice. When the mice were fed small amounts of antibiotic, theysuccessfully produced modified GLP1, which lasted for three months, and showed higher levels of insulin and lower levels of glucose.

The researchers also tested feeding the mice a high-fat diet. Compared to controls, the mice with modified GLP1 skin grafts put on less weight.

Dr Wu said the skin graft method could be safer than using engineered viral vectorsto edit genes in patient's own tyissues, as viruses 'may cause a very strong immune reaction and inflammation in vivo.' He added that lab-grown skin grafts have been used clinically for some time to treat burns, and have been proven safe.

Being able to control the gene expression using a drug would also allow doctors to calibrate how much of the enzyme enters a patients bloodstream.

'We think this can provide a long-term safe option for the treatment of many diseases,' Dr Wu said. 'It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect, such as haemophilia. Or it could function as a metabolic sink, removing various toxins.'

Dr Jeffrey Millman of Washington University, St Louis, who was not involved in the study, told The Scientist that more research would be needed to ensure that neither the CRISPR editing nor the stem cell culturing method inadvertently introduce dangerous mutations.

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Gene therapy skin grafts for obesity and diabetes - BioNews

Johns Hopkins researchers, working with an international consortium, say they have generated stem cells from skin cells from a person with a severe, early-onset form of Huntingtons disease (HD), and turned them into neurons that degenerate just like those affected by the fatal inherited disorder.

By creating HD in a dish, the researchers say they have taken a major step forward in efforts to better understand what disables and kills the cells in people with HD, and to test the effects of potential drug therapies on cells that are otherwise locked deep in the brain.

Although the autosomal dominant gene mutation responsible for HD was identified in 1993, there is no cure. No treatments are available even to slow its progression.

The research, published in the journal Cell Stem Cell, is the work of a Huntingtons Disease iPSC Consortium, including scientists from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, as well as six other groups. The consortium studied several other HD cell lines and control cell lines in order to make sure results were consistent and reproducible in different labs.

The general midlife onset and progressive brain damage of HD are especially cruel, slowly causing jerky, twitch-like movements, lack of muscle control, psychiatric disorders and dementia, and eventually death. In some cases (as in the patient who donated the material for the cells made at Johns Hopkins), the disease can strike earlier, even in childhood.

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

Ross and his team, as well as other collaborators at Johns Hopkins and Emory University, are already testing small molecules for the ability to block HD iPSC degeneration. These small molecules have the potential to be developed into novel drugs for HD.

The ability to generate from stem cells the same neurons found in Huntingtons disease may also have implications for similar research in other neurodegenerative diseases such as Alzheimers and Parkinsons.

To conduct their experiment, Ross took a skin biopsy from a patient with very early onset HD. When seen by Ross at the HD Center at Hopkins, the patient was just seven years old. She had a very severe form of the disease, which rarely appears in childhood, and of the mutation that causes it. Using cells from a patient with a more rapidly progressing form of the disease gave Ross team the best tools with which to replicate HD in a way that is applicable to patients with all forms of HD.

Her skin cells were grown in culture and then reprogrammed by the lab of Hongjun Song, Ph.D., a professor at Johns Hopkins Institute for Cell Engineering, into induced pluripotent stem cells. A second cell line was generated in an identical fashion in Dr. Rosss lab from someone without HD. Simultaneously, other HD and control iPS cell lines were generated as part of the NINDS funded HD iPS cell consortium.

Scientists at Johns Hopkins and other consortium labs converted those cells into generic neurons and then into medium spiny neurons, a process that took three months. What they found was that the medium spiny neurons deriving from HD cells behaved just as they expected medium spiny neurons from an HD patient would. They showed rapid degeneration when cultured in the lab using basic culture medium without extensive supporting nutrients. By contrast, control cell lines did not show neuronal degeneration.

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

Specifically, the damage caused by HD is due to a mutation in the huntingtin gene (HTT), which leads to the production of an abnormal and toxic version of the huntingtin protein. Although all of the cells in a person with HD contain the mutation, HD mainly targets the medium spiny neurons in the striatum, part of the brains basal ganglia that coordinates movement, thought and emotion. The ability to work directly with human medium spiny neurons is the best way, researchers believe, to determine why these specific cells are susceptible to cell stress and degeneration and, in turn, to help find a way to halt progression of HD.

Much HD research is conducted in mice. And while mouse models have been helpful in understanding some aspects of the disease, researchers say nothing compares with being able to study actual human neurons affected by HD.

For years, scientists have been excited about the prospect of making breakthroughs in curing disease through the use of stem cells, which have the remarkable potential to develop into many different cell types. In the form of embryonic stem cells, they do so naturally during gestation and early life. In recent years, researchers have been able to produce induced pluripotent stem cells (iPSCs), which are adult cells (like the skin cells used in Rosss experiments) that have been genetically reprogrammed back to the most primitive state. In this state, under the right circumstances, they can then develop into most or all of the 200 cell types in the human body.

The other members of the research consortium include the University of Wisconsin School of Medicine, Massachusetts General Hospital and Harvard Medical School, the University of California, San Francisco, Cardiff University the Universita degli Studi diMilano and the CHDI Foundation.

Primary support for this research came from an American Recovery and Reinvestment Act (ARRA) grant (RC2-NS069422) from the National Institutes of Healths National Institute of Neurological Disorders and Stroke and a grant from the CHDI Foundation, Inc.

Other Johns Hopkins researchers involved in this study include Sergey Akimov, Ph.D.; Nicolas Arbez, Ph.D.; Tarja Juopperi, D.V.M., Ph.D.; Tamara Ratovitski; Jason H. Chiang; Woon Roung Kim; Eka Chighladze, M.S., M.B.A.; Chun Zhong; Georgia Makri; Robert N. Cole; Russell L. Margolis, M.D.; and Guoli Ming, M.D., Ph.D.

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Turning Skin Cells Into Brain Cells - 06/28/2012

"By using our novel nanochip technology, injured or compromised organs can be replaced, said Dr Sen.

We have shown that skin is a fertile land where we can grow the elements of any organ that is declining.

TNT extends the concept known as gene therapy, which has been known about for some time, however the big difference is how the DNA is delivered into the body.

"The concept is very simple," said Professor James Lee, who co-led the research.

"As a matter of fact, we were even surprised how it worked so well.

In my lab, we have ongoing research trying to understand the mechanism and do even better.

So, this is the beginning, more to come."

"By using our novel nanochip technology, injured or compromised organs can be replaced. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining, said Dr Sen.

The study is published in the journal Nature Nanotechnology.

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Penny-sized nanochip pad to regrow organs and heal injuries - Telegraph.co.uk