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

Skin Stem Cells Comments Off on Skin transplants could treat diabetes and obesity – Futurity – Futurity: Research News | August 11th, 2017

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

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Chip reprograms skin cells with a short electric pulse - New Atlas - New Atlas

Skin Stem Cells Comments Off on Chip reprograms skin cells with a short electric pulse – New Atlas – New Atlas | August 10th, 2017

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

Skin Stem Cells Comments Off on Gene therapy via skin could treat diseases such as obesity – UChicago News | August 10th, 2017

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

Skin Stem Cells Comments Off on Stem cells: science prepares to take the first sip from the real fountain of youth – Catholic Online | August 9th, 2017

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

Skin Stem Cells Comments Off on Dramatic Burn-Healing Through Stem Cell Treatment – Fox Weekly | August 9th, 2017

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

Skin Stem Cells Comments Off on Wild new microchip tech could grow brain cells on your skin – CNET | August 9th, 2017

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

Skin Stem Cells Comments Off on A Chip That Reprograms Cells Helps Healing, At Least In Mice – NPR | August 9th, 2017

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

Skin Stem Cells Comments Off on Amniotic sac in a dish: Stem cells form structures that may aid of … – Phys.Org | August 9th, 2017

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

Skin Stem Cells Comments Off on Nanochip could heal injuries or regrow organs with one touch, say researchers – The Guardian | August 8th, 2017

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

Skin Stem Cells Comments Off on CRISPR Skin Grafts Could Replace Insulin Shots For Diabetes – Futurism | August 8th, 2017

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

Skin Stem Cells Comments Off on Turning Skin Cells Into Brain Cells – 06/28/2012 | August 7th, 2017

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

Skin Stem Cells Comments Off on Gene therapy skin grafts for obesity and diabetes – BioNews | August 7th, 2017

Stem cells have been cultured to treat many different of conditions

Lewis Houghton/Science Photo Library

By Andy Coghlan

Last week, two people with type 1 diabetes became the first to receive implants containing cells generated from embryonic stem cells to treat their condition. The hope is that when blood sugar levels rise, the implants will release insulin to restore them to normal.

About 10 per cent of the 422 million people who have diabetes worldwide have type 1 diabetes, which is caused by the bodys immune system mistakenly attacking cells in the pancreas that make insulin. For more than 15 years, researchers have been trying to find a way to use stem cells to replace these, but there have been several hurdles not least, how to get the cells to work in the body.

Viacyte, a company in San Diego, California, is trying a way to get round this. The firms thumbnail-sized implant, called PEC-Direct, contain cells derived from stem cells that can mature inside the body into the specialised islet cells that get destroyed in type 1 diabetes.

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The implant sits just below the skin, in the forearm, for example, and is intended to automatically compensate for the missing islet cells, releasing insulin when blood sugar levels get too high.

If it works, we would call it a functional cure, says Paul Laikind, of Viacyte. Its not truly a cure because we wouldnt address the autoimmune cause of the disease, but we would be replacing the missing cells.

The device has already been safety tested in 19 people with diabetes, using smaller numbers of stem cells. Once implanted, the progenitor cells housed in the device did mature into islet cells, but the trial didnt use enough stem cells to try to treat the condition.

Now Viacyte has implanted PEC-Direct packages containing more cells into two people with type 1 diabetes. A third person will also get the implant in the near future. Once inside the body, pores in the outer fabric of the device allow blood vessels to penetrate inside, nourishing the islet progenitor cells and exposing them to growth factors that push them to mature. Once these cells have matured which should take about three months the hope is that they will be able to monitor sugar levels in the blood, and release insulin as required.

If effective, it could free people with type 1 diabetes from having to closely monitor their blood sugar levels and inject insulin, although they would need to take immunosuppressive drugs to stop their bodies from destroying the new cells.

If successful, this strategy could really change the way we treat type 1 diabetes in the future, says Emily Burns of the charity Diabetes UK. A similar way to treat the condition with pancreas cells from organ donors has been in use for nearly 20 years, successfully freeing recipients from insulin injections, but a shortage of donors limits how many people are able to have this treatment.

This isnt a problem with stem cells. The embryonic stem cells used to make the progenitor cells originally came from a spare early stage embryo donated by a woman who was having IVF. Because embryonic stem cells, and the progenitor cells made from them, can be multiplied in limitless amounts, Laikand says that, if the treatment works, the method would be able to treat everyone who has the condition.

A limitless source of human insulin-producing cells would be a major step forward on the journey to a potential cure for diabetes, says James Shapiro at the University of Alberta, Canada, who has collaborated with Viacyte on this project, and who pioneered the donor pancreas method decades ago. For sure, this will in the end prove to be a durable landmark for progress in diabetes care.

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First implants of stem-cell pouches to 'cure' type 1 diabetes - New Scientist

Skin Stem Cells Comments Off on First implants of stem-cell pouches to ‘cure’ type 1 diabetes – New Scientist | August 7th, 2017

Injured tissues can be repaired and damaged organs healed using a new nanotech device that adapts a patients own skin to generate stem cells, according to a paper published in the journal Nature Nanotechnology.

Researchers from Ohio State University call the new technology tissue nanotransfection (TNT).

They say TNT which is basically a lab on a chip can adapt skin cells to change into any type of tissue required, which can then be introduced to injured or degenerated areas. They claim a success rate of 98%.

With this technology we can convert skin cells into elements of any organ with just one touch, says co-author Chandan Sen. 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."

Lead author Daniel Gallego-Perez says the new technology comprises two elements: the nanotech chip designed to introduce reprogrammed DNA into existing adult cells; and a specific biological cargo that induces the cells to change from one type to another.

The device works using a small electrical charge.

It does not require any laboratory-based procedures, according to Gallego-Perez, and can be used at the point of care a doctors office, say, or an outpatient clinic.

The paper describes experiments on mice and pigs. These included using the device to act upon badly injured legs that lacked blood flow. One week after the application of TNT, vascular vessels reappeared. Within a fortnight flow was back within normal parameters.

In a second experiment, skin cells were converted into nerve cells and introduced into the brains of mice crippled by stroke.

Says Sen: 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.

The concept is very simple, adds co-author James Lee: 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.

Lee, Sen and Gallego-Perez were part of a group of researchers that lodged a patent application in 2016 for an earlier iteration of TNT: a device that enables compositions and methods for reprogramming somatic cells into induced endothelial cells.

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Nano-chip promises to heal organs at a touch - Cosmos

Skin Stem Cells Comments Off on Nano-chip promises to heal organs at a touch – Cosmos | August 7th, 2017

"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

Skin Stem Cells Comments Off on Penny-sized nanochip pad to regrow organs and heal injuries – Telegraph.co.uk | August 7th, 2017

What causes the body to age?

The Greek Philosopher Aristotle thought it was the hearta hot, dry organ at the seat of intelligence, motion and sensation.

Fast-forward a few centuries, and the brain has overthrown the heart as master of thought. But its control over bodily agingif anywas unclear. Because each organ has its own pool of stem cells to replenish aged tissue, scientists have long thought that the body has multiple aging clocks running concurrently.

As it turns out, thats not quite right.

This week, a study published in Nature threw a wrench into the classical theory of aging. In a technical tour-de-force, a team led by Dr. Dongsheng Cai from the Albert Einstein College of Medicine pinpointed a critical source of aging to a small group of stem cells within the hypothalamusan ancient brain region that controls bodily functions such as temperature and appetite.

Like fountains of youth, these stem cells release tiny fatty bubbles filled with mixtures of small biological molecules called microRNAs. With age, these cells die out, and the animals muscle, skin and brain function declines.

However, when the team transplanted these stem cells from young animals into a middle-aged one, they slowed aging. The recipient mice were smarter, more sociable and had better muscle function. Andget thisthey also lived 10 to 15 percent longer than mice transplanted with other cell types.

To Dr. David Sinclair, an aging expert at Harvard Medical School, the findings represent a breakthrough in aging research.

The brain controls aging, he says. I can see a day when we are implanted with stem cells or treated with stem cell RNAs that improve our health and extend our lives.

Its incredible to think that a tiny group of cells in one brain region could be the key to aging.

But to Cai, there are plenty of examples throughout evolution that support the theory. Experimentally changing a few of the 302 neurons in the nematode worm C. elegans is often sufficient for changing its lifespan, he says.

Of course, a mammalian brain is much more complicated than a simple worm. To narrow the problem down, Cai decided to zero in on the hypothalamus.

The hypothalamus has a classical function to regulate the whole bodys physiology, he says, so theres a natural logic for us to reason that the hypothalamus might be involved in aging, which was never studied before.

Even so, it was a high-risk bet. The hippocampusbecause of its importance in maintaining memory with ageis the most popular research target. And while the hypothalamus was previously somehow linked to aging, no one knew how.

Cais bet paid off. In a groundbreaking paper published in 2013, he found that a molecule called NF-kappaB increased in the hypothalamus as an animal grew older. Zap out NF-kappaB activity in mice, and they showed much fewer age-related symptoms as they grew older.

But heres the kicker: the effects werent limited to brain function. The animals also better preserved their muscle strength, skin thickness, bone and tendon integrity. In other words, by changing molecules in a single part of the brain, the team slowed down signs of aging in the peripheral body.

But to Cai, he had only solved part of the aging puzzle.

At the cellular level, a cornucopia of factors control aging. There is no the key to aging, no single molecule or pathway that dominates the process. Inflammation, which NF-kappaB regulates, is a big contributor. As is the length of telomeres, the protective end caps of DNA, and of course, stem cells.

Compared to other tissues in the body, stem cells in the brain are extremely rare. So imagine Cais excitement when, just a few years ago, he learned that the hypothalamus contains these nuggets of youth.

Now we can put the two threads together, and ask whether stem cells in the hypothalamus somehow regulate aging, he says.

In the first series of experiments, his team found that these stem cells, which line a V-shaped region of the hypothalamus, disappear as an animal ages.

To see whether declined stem cell function contributes to aging, rather as a result of old age, the researchers used two different types of toxins to wipe out 70 percent of stem cells while keeping mature neurons intact.

The results were striking. Over a period of four months, these mice aged much faster: their muscle endurance, coordination and treadmill performance tanked. Mentally, they had trouble navigating a water maze and showed less interest in socializing with other mice.

All of these physiological changes reflected an acceleration in aging, Cai and team concluded in their article.

And the consequences were dire: the animals died months earlier than similar transgenic animals without the toxin treatment.

If the decline in stem cell function is to blame for aging, then resupplying the aged brain with a fresh source of stem cells should be able to reinvigorate the animal.

To test this idea, the team isolated stem cells from the hippocampus of newborn mice, and tinkered with their genes so that they were more resilient to inflammation.

We know the aged hypothalamus has more inflammation and that hurts stem cells, so this step was necessary, explained the authors.

When transplanted into middle-aged mice, they showed better cognitive and muscular function four months later. Whats more, they lived, on average, 10 percent longer than mice transplanted with other cell types. For a human, that means extending an 85-year life expectancy into 93. Not too shabby.

But the best was yet to come. How can a few cells have such a remarkable effect on aging? In a series of follow-up experiments, the team found that the pool of biological molecules called microRNAs was to thank.

microRNAs are tiny molecules with gigantic influence. They come in various flavors, bearing rather unimaginative names like 106a-5p, 20a-5p and so on. But because they can act on multiple genes at the same time, they pack a big punch. A single type of microRNA can change the way a cell workswhether it activates certain signaling pathways or makes certain proteins, for example.

While most cells make microRNAs, Cai found that the hypothalamus stem cells have a unique, very strong ability to pack these molecules up into blobs of membrane and shoot them out like a bubble gun.

Once outside the cell, the microRNAs go on a fantastic voyage across the brain and body, where they tweak the biology of other tissues.

In fact, when the team injected purified little bubbles of microRNAs into middle-aged mice, they also saw broad rejuvenating effects.

Cai explains: we dont know if the microRNAs are pumped out to directly affect the rest of the body, or if they first act on different areas of the brain, and the brain goes on to regulate aging in the body.

Even so, the aging field is intrigued.

According to Dr. Leonard Guarente, an aging biologist at MIT, the study could lead to new ways to develop anti-aging therapies.

Whats more, its possible the intervention could stack with other known rejuvenating methods, such as metformin, young blood or molecules that clean out malfunctioning cells.

Its possible that stem-cell therapy could boost the hypothalamus ability to regulate aging. However, scientists still need to know how stem cells link with the hypothalamus other main role, that is, releasing hormones.

Of course, injecting cells into the brain isnt a practical treatment. The team is now working hard to identify which of the thousands of types of microRNAs control aging and what exactly they do.

Then the goal is to validate those candidate anti-aging microRNAs in primates, and eventually, humans.

Of course humans are more complex. However, if the mechanism is fundamental, you might expect to see effects when an intervention is based on it, says Cai.

Stock Media provided by digitalreflections / Pond5

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Breakthrough Stem Cell Study Offers New Clues to Reversing Aging - Singularity Hub

Skin Stem Cells Comments Off on Breakthrough Stem Cell Study Offers New Clues to Reversing Aging – Singularity Hub | August 6th, 2017

Very few people have ever heard ofthe concept of artificial skin transplants.That will change in the near future, though. Artificial skin transplants may be the one thing we need most to treat type 2 diabetes. The skin grafts based on CRISPR gene editing couldyield some very powerful results. Their first tests involving mice werepositive, butensuring the technology works for humans in the same way will besomething else entirely.

Alot of people may not like the sound of artificial skin transplants. It sounds a lot scarier than it really is, however. There is actually nothing to fear about them. In fact, we have been using artificial skin implants for several decades now.Burn patients often recover thanks to these implants, for example. Artificial skin implants have proven to be an invaluable tool in the world of healthcare so far, and it seems thenumber of use cases may be expanded upon. However,they havenever been deployed to treat diabetesup untilnow.

Scientists have now successfully used these implants to treat diabetes in mice. That is a major development in medicine. The researchers edited stem cells from newborn mice to control the release of ahormone stimulating insulin production. Once the cells were turned into skin grafts, they were given to mice suffering from diabetes.

The mice were not born with diabetes. Instead, researchers fed them high-fat diets to causeobesity. Acruel method, perhaps, thoughit is not uncommon to see this sort of thingin the medical sector. Obesity is still one of the main risk factors causing type 2 diabetes in humans. People with a high insulin resistance are particularly prone to developing thecondition. Diabeteswas induced in these mice usingsome modifications to create viable test criteria.

Once the mice received the artificial skin implants, their insulin resistance levels started to reverse. Additionally, they gained around half the weight as those not given the grafts. Thissuggests that people cantreat diabetes usingthese implants, although theywill not do much for anyone suffering from type 1 diabetes. Thosewho do suffer from that condition may soon have access to a cheap and efficient solution created from stem cells. The goal is to turn these stem cells into human skin over time.

There may be other clinical applicationsinvolving artificial skin implants we have yet to discover. Ever since doctors started treating burn patients with this technique, the quest to find other use cases has been in full effect. Thanks torecent breakthroughsin this field, one can now grow artificial skin in a lab. However, given the lack of human test subjects, finding other use cases has been pretty difficult. This is where the mice come into the picture, even though the results involving human subjects mightdiffer greatly.

This is not a cure for diabetes, but it is an approach to help people maintain their glucose levels. For now, it only works withtype 2 diabetes causedby obesity, but it is still an important breakthrough regardless. The bigger question is what other types of diseases may be treated through artificial skin implants.

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Scientists Use Artificial Skin Implants to Treat Type 2 Diabetes The ... - The Merkle

Skin Stem Cells Comments Off on Scientists Use Artificial Skin Implants to Treat Type 2 Diabetes The … – The Merkle | August 6th, 2017

Genetically engineered skin cells grafted onto mice can treat the animals diabetes and obesity, according to new research published August 2, 2017 in Cell Stem Cell.

Researchers edited skin stem cells from newborn mice using CRISPR-based technology so that the cells secreted a peptide that regulates blood sugar. Transplanting the cells onto mice showed the grafts increased insulin secretion and reversed weight gain from a high-fat diet, as well as overturned insulin resistance. The result is a small step toward developing a safe and durable gene therapy to treat diabetes in humans.

Weve had this idea for a long time, so its exciting to see that, indeed, it can work to deliver therapeutics, coauthor Xiaoyang Wu, a stem cell biologist at the University of Chicago, tells GEN.

In the study, Wu and colleagues worked with skin because it is a large organ and easily accessible. The cells multiply quickly and are easily transplanted. And, transplanted cells can be removed, if needed. Skin is such a beautiful system, Wu says, noting that its features make it a perfect medium for testing gene therapies.

The team worked with the gene that produces glucagon-like peptide 1 (GLP-1), a hormone that stimulates the pancreas to secrete insulin. The additional insulin takes excessive glucose out of the bloodstream, which regulates complications from diabetes. The hormone can also decrease appetite. Using the genetic engineering tool CRISPR, the team inserted a mutation, adding an antibody fragment to the gene that would make the GLP-1 last longer in the blood and an additional modification to the targeting vector that would also attach an inducible promoter. This switch turns the gene on, as needed, to make more GLP-1. The switch would be triggered by the administration of the antibiotic doxycycline.

Wu and colleagues then inserted the altered gene into skin cells and grew the cells in a culture. Once the skin cells had grown into multiple layers, the team transplanted the patches onto mice with intact immune systems. Surprisingly, the mice didnt reject the graftsa feat in itselfsince human skin transplants are far more advanced than mice grafts, partly due to the animals furry skin.

Next, the team fed the mice small amounts of doxycycline. As a result, the animals released GLP-1 into the blood and had higher levels of insulin and lower levels of glucose. When fed a high-fat diet, the mice gained weight and became obese. But when the mice also were fed doxycycline so they secreted GLP-1, they gained less weight, showing the gene therapy was successful.

This kind of therapy could be potentially effective for many metabolic disorders, Wu says. The grafts could be used in patients who cant process protein or in individuals with hemophilia. The team is now testing the gene-therapy technique in combination with other medications.

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CRISPR Gene Therapy via Skin Grafts Treats Obesity and Diabetes in Mice - Genetic Engineering & Biotechnology News

Skin Stem Cells Comments Off on CRISPR Gene Therapy via Skin Grafts Treats Obesity and Diabetes in Mice – Genetic Engineering & Biotechnology News | August 6th, 2017

The secret to healing what ails you lies within your own DNA.(photo credit:DREAMSTIME)

Scientists have, for the first time, corrected a disease-causing mutation in early-stage human embryos using gene editing.

The technique, which uses the CRISPR- Cas9 system, corrected the mutation for a heart condition at the earliest stage of embryonic development so that the defect would not be passed on to future generations.

It could pave the way for improved in vitro fertilization outcomes as well as eventual cures for some thousands of diseases caused by mutations in single genes.

The breakthrough and accomplishment by American and Korean scientists, was recently explained in the journal Nature. Its a collaboration between the Salk Institute, Oregon Health and Science University and South Koreas Institute for Basic Science.

Thanks to advances in stem cell technologies and gene editing, we are finally starting to address disease-causing mutations that impact potentially millions of people, said Prof. Juan Carlos Izpisua Belmonte of Salks gene expression lab and a corresponding author of the paper. Gene editing is still in its infancy, so even though this preliminary effort was found to be safe and effective, it is crucial that we continue to proceed with the utmost caution, paying the highest attention to ethical considerations.

Though gene-editing tools have the power to potentially cure a number of diseases, scientists have proceeded cautiously partly to avoid introducing unintended mutations into the germ line (cells that become eggs or sperm).

Izpisua Belmonte is uniquely qualified to speak on the ethics of genome editing because, as a member of the Committee on Human Gene Editing at the US National Academies of Sciences, Engineering and Medicine, he helped author the 2016 roadmap Human Genome Editing: Science, Ethics and Governance.

Hypertrophic cardiomyopathy is the most common cause of sudden death in otherwise healthy young athletes, and affects approximately one in 500 people. It is caused by a dominant mutation in the MYBPC3 gene, but often goes undetected until it is too late. Since people with a mutant copy of the MYBPC3 gene have a 50% chance of passing it on to their own children, being able to correct the mutation in embryos would prevent the disease not only in affected children but also in their descendants.

The researchers generated induced pluripotent stem cells from a skin biopsy donated by a male with Hypertrophic cardiomyopathy and developed a gene-editing strategy based on CRISPR-Cas9 that would specifically target the mutated copy of the MYBPC3 gene for repair. The targeted mutated MYBPC3 gene was cut by the Cas9 enzyme, allowing the donors cells own DNA -repair mechanisms to fix the mutation during the next round of cell division by using either a synthetic DNA sequence or the non-mutated copy of MYBPC3 gene as a template.

Using IVF techniques, the researchers injected the best-performing gene-editing components into healthy donor eggs that are newly fertilized with donors sperm. All the cells in the early embryos are then analyzed at single-cell resolution to see how effectively the mutation was repaired.

They were surprised by the safety and efficiency of the method. Not only were a high percentage of embryonic cells get fixed, but also gene correction didnt induce any detectable off-target mutations and genome instability major concerns for gene editing.

The researchers also developed an effective strategy to ensure the repair occurred consistently in all the cells of the embryo, as incomplete repairs can lead to some cells continuing to carry the mutation.

Even though the success rate in patient cells cultured in a dish was low, we saw that the gene correction seems to be very robust in embryos of which one copy of the MYBPC3 gene is mutated, said Jun Wu, a Salk staff scientist and one of the authors.

This was in part because, after CRISPR- Cas9 mediated enzymatic cutting of the mutated gene copy, the embryo initiated its own repairs. Instead of using the provided synthetic DNA template, the team surprisingly found that the embryo preferentially used the available healthy copy of the gene to repair the mutated part.

Our technology successfully repairs the disease-causing gene mutation by taking advantage of a DNA repair response unique to early embryos, said Wu.

The authors emphasized that although promising, these are very preliminary results and more research will need to be done to ensure no unintended effects occur.

Our results demonstrate the great potential of embryonic gene editing, but we must continue to realistically assess the risks as well as the benefits, they added.

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Early gene-editing holds promise for preventing inherited diseases - The Jerusalem Post

Skin Stem Cells Comments Off on Early gene-editing holds promise for preventing inherited diseases – The Jerusalem Post | August 6th, 2017

Most nights, Marcia Dunlap attaches seven or eight leeches around her husband John's eyes as part of an effort to restore some of his vision. Tom Bailey/The Commercial Appeal

With the help of his wife Marcia, John Dunlap receives his nightly leech treatment at his home in East Memphis. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

At home most evenings, Memphis, Tennessee, attorney John Dunlap, 80, unbuttons and removes his white dress shirt and counting his steps and remembering which way to turn carefullywalks with a tall white canefrom the living room to the dining table, where his wife Marcia has a plastic container of leeches.

Twenty-six months ago,the couple's schizophrenic sonAndrewattacked them in theirhome. The injuries blinded Dunlap. He's in total darkness.

After drapinga large, peach-colored towel around John's neck, Marcia reaches into the water for the skinniest leeches. Those are the hungriest and most likely to latchonto John's face.

One at a time, she gently presses four leeches to the skin around John's left eye and three around the right. She waits patiently wait for eachto bite and stay connected to John's skin.

"You can feel a bite,'' he says. "A little, stinging bite... And then after awhile you don't feel anything.''

The Dunlaps have carried out this unusualroutine60 or so times since December. It's a type of therapy prescribed by a Los Angeles doctor who offers experimental stem cell therapy designed to regenerate tissue.

"In the beginning he made it very clear he's not anophthalmologist and not an eye surgeon but he had had some success with stem cells in treating blindness. It's experimental,'' Dunlap said.

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The doctor prescribed the leech therapy as a preliminary step because, Dunlap said, the leech enzymesenhance the blood supply to the eye and nourishthe eye tissue.

The left eye had atrophied, or withered. The idea wasto restore health to the eyebefore the stem cell treatment. There is no right eye, but the hope is that the leech enzymes will help revive that optic nerve in case a transplant is ever possible.

Since the leech therapy,the pressure in the right eye has improved significantly, Dunlapsaid, referring to follow-upexams. The retina, which had folded into an ice-cream cone shape after the trauma, has begun returning to its normal shape, he said.

Even though he still cannot see out of the left eye and the optic nerve remains severed from the retina, Dunlap said, "I now have a live eye.''

The Dunlaps decline to identify the California doctor, describing him as a"humble'' person whodoes not seek the publicity.

With the help of his wife Marcia, John Dunlap receives his nightly leech treatment at his home in East Memphis. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

Andrew, the Dunlaps' mentally ill son, is charged with attempted murder and domestic assault, and remains in jail awaiting trial. Thecouplehave told authorities that they mainly want Andrew to receive mental health treatment.

The Dunlapshave experienced tragedy long before the 2015 assault.

Their son Jeff, one of four children, was a St. Jude Children's Research Hospital patient who died of cancer at age 10, in September 1974.

Dunlap recalls a return car tripfrom Knoxville, where he and Marcia had been visiting grandchildren shortly after he was released from rehab.

"As we were driving back I started thinking of all the things I won't get to do again. In my mind, I was going down the list,'' he said.

It would be a long list, including some leisure activities he loves. An avid Cubs fan, heenjoyed attending spring training games in Arizona. A passionate golfer, he enjoyedwatching how the ball flew when he struck it well.

But Dunlap stopped himself from completing the list of losses, telling himself, " 'You don't want to dwell on that'. . . It's as if the Lord sent me a message that hit me across my forehead, saying, 'John, get over it. It could be a whole lot worse.'

"Anytime I want to start thinking about the things I'm missing or not doing what I used to do, I think 'Get over it. Move on'.''

Sudden blindness is such a change in lifestyle. "I guess some people may feel the world has ended for them, but it hasn't,'' he said.

Marcia Dunlap gets special leeches for her husband John's nightly treatment from the laundry room where she keeps it out of sight. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

The stem cell and leech therapy is expensive and not covered by health insurance. Some have expressed their skepticism about the legitimacy of the experimental treatments.

"You have some people who are concerned for you, that your approach is not going to be effective,'' Dunlap said.

"Yet, several folks up herehave said, 'John, I'd take a shot at it. It is expensive but you're the one with the white cane and the one who is blind and has to live with it. You have everything to gain and nothing to lose.'''

While some might be concerned about the unusual treatments, many others are inspired by the Dunlaps,saidBlanche Tosh, a fellow church member and friend since high school.

"I have told them so many times, 'You just can't begin to know the lives you have affected,'' Tosh said.

"I know so many people who look at the way they are dealing with multiple things. How could anybody endure that and just go on and be pleasant and make it from day to day with the consistent attitude that the world sees.

"You are not going to find many people whoever see one of them without a smile,'' Tosh said.

She was inspired to start a gofundme account (gofundme.com/johndunlapvision) to help coverthe Dunlaps' expenses. As of midweek, $8,795 of the $100,000 goal had been raised.

Memphis lawyer John Dunlap and his wife Marcia continue to search for some medical procedure to restore at least partial vision after John was blinded a few years ago when their mentally ill son attacked him. (Photo: Jim Weber/The Commercial Appeal)

Since December, Dunlap has undergone two-and-a-half rounds of leech therapy and two series ofstem cell treatments. The couple traveled to California in June for the most recent stem cell procedures, and returned home with stem-cell eye drops and injections.

Nowthey are in the middle of the leech therapy they resumed this summer.

John has a follow-up exam next week, when he will learn if there's been continued progress from the stem cell and leech therapies.

The California doctor "indicated it would take two to three months to see if we were getting any results from stem cell therapy out there,'' Dunlap said. That time could come sometime this month or in September.

If the stem cell therapy has not worked by then, he said,"We'll just have to see what any third plan looks like, and the cost involved.''

Late in life, Dunlap has been forced to learn to type, work a computer, navigate with a cane, count the steps and memorize the turns from one spot to another, communicate with Siri, and smile as blood-sucking leeches dangle from his cheeks.

Asked about his sources of inner-strength, he responded, "I don't know I'd call it inner-strength.

"I can tell you I certainly believe in the Lord. We pray daily. I appreciate the prayers of others. I think it certainly is a faithissue.''

He also credits his late mother, Cora, a single parentwho managed a grocery. "She was a very optimistic, loving person,'' he recalled.

"And I've had Marcia's support. Marcia wasn't going to let me give up, just sit down and do nothing.''

The Dunlaps are starting to consider resuming their annual trips to Cubs spring training in Arizona. Maybe next spring.

"You may have your vision by then,'' Marcia told John.

"I might,'' he responded."We'll see.''

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Will putting leeches on his face help this blind man see? - USA TODAY

Skin Stem Cells Comments Off on Will putting leeches on his face help this blind man see? – USA TODAY | August 5th, 2017