"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

If you look at your skin, most of what you will see is actually dead cells. This thin outermost sheet protects the living cells underneath as they develop.

Thats why people exfoliatebecause your skin cells are designed to mature and slough off, says Thierry Work, a wildlife disease specialist with the U.S. Geological Survey. In June, he and his colleagues reported that they successfully mimicked this process with sea turtle skin. No, they didn't give sea turtles a facial, but they did grow layers of turtle skin in the lab.

Work is studying the virus responsible for a deadly disease called fibropapillomatosis, which causes tumors to grow all over sea turtles skin and inside their bodies. In order to grow this virus we have to basically replicate skin in the lab, because this virus will only grow when skin cells are maturing, he says. Cultivating the elusive virus may help researchers save sea turtles and perhaps shed light on how herpes viruses replicate in people.

Works efforts represent the first time that scientists have engineered reptile skin, but weve been building our own lab-grown versions of mammalian skin for decades. Lab-made skin can help us find treatments for diseases, heal wounds, spare animals from cosmetics testing, and design leather that emulates the look and feel of real animal hides. Heres how were imitating skin to benefit humans and other creatures.

Turtle trouble

Fibropapillomatosis most often strikes endangered green turtles, although it sometimes shows up in other species of sea turtles. The illness can debilitate turtles by growing tumors that prevent the animals from seeing properly or eating, and by suppressing the immune system.

To combat this disease, scientists must examine how the virus (Chelonid herpesvirus 5, or ChHV5 for short) multiplies in living cells. So Work and his team collected skin samples from green turtles with fibropapillomatosis that had just died or had to be euthanized. They then made a gel from collagenthe same protein that gives skin its firmnessand seeded it with cells taken from deep within the donated skin. Its this layer that we see when we examine a leather handbag or pair of shoes, Work says. Finally, his team grew surface skin cells on top of this scaffold.

The fruits of their labors are little plugs of skin only about 5 to 6 millimeters wide. But under the microscope, they look just like actual turtle skin, Work says.

Chelonid herpesvirus 5 and some other viruses (such as the one that causes warts in people) cant be grown in a lab without an environment that mimics the shape of skin and is populated by live, maturing cells.

Other viruses are less demanding, including herpes simplex (cause of cold sores and genital herpes in humans). Normally, herpes simplex and other viruses are grown on a flat lawn of skin cells in a petri dish. But this setting doesnt really recreate the shape and structure of real skin. So there may be insights were missing by cultivating viruses in a dish. We really havent seen what the virus does in the actual three-dimensional structure of reconstructed skin, Work says.

When he and his colleagues grew ChHV5 in their turtle skin, the pathogen did not behave as expected. The viruses formed odd looking, sun-shaped structures to serve as factories in the cells where the virus settled in and made copies of itself. The way all these components were being put togetherwas quite different than what people saw with conventional herpes viruses, Work says.

It could be that herpes simplex, and other herpes viruses that infect people, also form similar structures to assemble fresh recruits. The replication of the herpes virus is actually a lot more complicated than what people thought, Work speculates. The more we know about how viruses actually interact with cells, the more effective drugs we can design.

Now that scientists can cultivate ChHV5 in the lab, the next step is to come up with a blood test for fibropapillomatosis. That would tip them off that the disease is on the loose in a particular area before turtles begin to die. Theyre in a world of hurt, and by the time theyre heavily tumored its really too late to do anything, Work says.

It wont be practical to vaccinate or treat all the turtles directly. But we may be able to discourage the diseases transmission, the same way we use insecticides and bed nets to thwart mosquitoes from passing on malaria.

And now that reptile skin has been successfully grown in the lab, the technique could be put to work investigating other reptile and amphibian skin diseases. Engineered hide might help us learn more about snake fungal disease, which threatens snakes in the eastern and Midwestern United States, or the chytrid fungus that has infected frogs around the globe.

Healing wounds

Turtle skin doesnt have hair follicles or sweat glands, Work says. So its a bit easier to engineer than human skin. Nevertheless, the technique he used to emulate sea turtle pelts was adapted from ones commonly used to grow our own version of human skin.

Skin substitutes are an alternative to using grafts transplanted from elsewhere on a patients body to cover burns or other chronic wounds. Theres going to be a limited number of times that patients will allow the grafts to be taken from their thighs. These products that are ready-made became very popular because of that, says Vincent Falanga, an emeritus professor in the Boston University School of Medicines department of dermatology, whose studies on living bioengineered skin led to the U.S. Food and Drug Administration approving it to help non-healing wounds close more quickly.

Unlike skin grafts, bioengineered skin does not stick around, and eventually disintegrates. It does, however, protect the wound and stimulate the skins natural healing processes. Using bioengineered skin is a less painful process than undergoing skin grafts and may cause fewer complications, although its also more costly in general.

Bioengineered skin is often grown using cells taken from newborns foreskins. However, the vigorous young cells may stimulate the damaged area so much that it requires more energy than it can supply, Falanga says. Bioengineered skin that relies on less-active adult cells might actually be more effective in helping wounds to heal.

Skin substitutes dont quite function like the real thing. Last year, though, researchers in Japan reported that theyd grown realistic mouse skin from stem cells and successfully transplanted it onto other rodents. Previously when scientists grew skin from stem cells, they only managed to make sheets of cells emulating the skins outermost layer. But the new skin recreated all three of the layers found in skin, as well as boasting hair follicles and sebaceous glands (which make a fatty secretion to lubricate the skin).

Falanga is skeptical that this kind of engineered skin will perform well in chronic wounds. People in the bioengineering field, they want to reproduce whats already in nature, he says. We want to have a product that looks exactly like skin. Yet lingering wounds lack proper blood supply or have other problems that prevent them from healing. So they may be unable to maintain normally functioning skin, with its high energy demands.

However, the team in Japan hopes their lab-grown skin will eventually help people with burns, scars, or skin diseases like alopecia. "Up until now, artificial skin development has been hampered by the fact that the skin lackedimportant organs, such as hair follicles and exocrine glands, coauthor Takashi Tsuji, of the RIKEN Center for Developmental Biology, said in a press release. With this new technique, we have successfully grown skin that replicates the function of normal tissue.

The realistic skin also brings scientists closer to their dream of growing whole organs that can be transplanted into people, Tsuji said.

Sparing animals

But medical treatments aren't the only uses for skin substitutes. Tsuji and his team also have another goal in mind for their creation: Eventually, the realistic skin could be used for testing out cosmetics in lieu of animals.

There are already several companies devoted to just this purpose. Boston-based MatTek sells their lab-grown skin to other companies that make laundry detergent, makeup, anti-aging creams, and other chemicals.

Like Works sea turtle skin, these nubbins of skin are tinyjust a fraction of a millimeter thick. They are grown from skin cells left over after surgical procedures like tummy tucks and circumcisions. This skin is a better proxy for actual human hide than animals are, one of MatTeks customers told Wired last year.

Lab-made skin will soon provide an alternative to leather, too. Brooklyn-based startup Modern Meadow genetically engineers animal cells to produce collagen, which they use to make leather that resembles actual animal pelts. The biofabricated leather takes two weeks to grow, as opposed to the years it takes to raise an animal, slaughter it, and tan its hide. And because the cell-spun leather lacks features like hair and fat, its more eco-friendly to treat than the real thing.

Could Works lab-grown reptile hide also be used instead of skin from actual snakes or alligators for bags and shoes? Youd need to optimize this technique quite a bit before you got to that scale, he says. But I certainly think its possible.

Also apparently on the table: using DNA from a deceased fashion icon to grow skin for leather jackets and bags. Designer Tina Gorjanc wants to create artificial skin using Alexander McQueens genetic material, harvested from hair he used in a 1992 collection. Shes filed a patent in the United Kingdom for the process, although for now her prototypes are made from pig leather treated to look like human skin.

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Growing skin in a lab has benefits for humans and turtles alike - Popular Science

Skin Stem Cells Comments Off on Growing skin in a lab has benefits for humans and turtles alike – Popular Science | August 5th, 2017

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EL PASO, Texas - Three new retailers are setting up shop inside Cielo Vista Mall.

Simon Properties announced the opening of three new stores: ThinkGeek, Adore Cosmetics, and Ooh La La.

Opening mid-August, ThinkGeek offers a wide assortment of "nerd interest-inspired" items, gadgets, apparel, and unique licensed products from pop culture brands like STAR WARS, Star Trek, Game of Thrones, Marvel, Nintendo, Minecraft, and various others.

The 2,172 square-foot store will be on the upper level, next to JCPenney.

Meanwhile, Ooh La La will give customers a number of options when it comes to snack foods. Specializing in traditional Mexican snacks, gift baskets and custom gift wrapping, the store will open mid-August next to LIDS.

Adore Cosmetics offers organic skin care products mostly powered by stem cells from plants. The cosmetics company's products are designed to "help reverse the signs of aging and restore a youthful glow to the skin be harnessing the power of nature," according to the store's description.

Slated to open late August, the store is located between Vitamin World and LIDS.

Shawn Thomson, General Manager of Cielo Vista Mall, says they are constantly searching for ways to keep new and veteran visitors happy.

"We are continually looking for opportunities to enhance our visitor's experience with a unique mix of retail offerings," Thomson said."We believe these new offerings will speak to our current customer base, giving them new options, while simultaneously attracting new customers to Cielo Vista Mall."

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ThinkGeek, Adore Cosmetics and Ohh La La coming to Cielo Vista Mall - KVIA El Paso

Skin Stem Cells Comments Off on ThinkGeek, Adore Cosmetics and Ohh La La coming to Cielo Vista Mall – KVIA El Paso | August 4th, 2017

THURSDAY, Aug. 3, 2017 (HealthDay News) -- Scientists have created genetically altered skin cells that may control type 2 diabetes in lab mice. And they believe the general concept could someday be used to treat various diseases.

Using a combination of stem cells and "gene editing," the researchers created patches of skin cells that were able to release a hormone called GLP1 in a controlled manner.

The hormone, which is normally produced in the digestive tract, spurs the production of insulin -- the body's key regulator of blood sugar levels.

The scientists found that transplanting the engineered skin patches onto diabetic lab mice helped regulate their blood sugar levels over four months.

Xiaoyang Wu, a stem cell biologist at the University of Chicago, led the "proof of concept" study. He said it raises the possibility that "therapeutic skin grafts" could be used to treat a range of diseases -- from hemophilia to drug dependence.

Wu's team focused on type 2 diabetes in these initial experiments because it's a common condition.

However, a researcher not involved in the study doubted the usefulness of the approach for diabetes specifically.

People with type 2 diabetes already manage the disease with diet, exercise and medications -- including ones that target GLP1, said Juan Dominguez-Bendala.

Using high-tech gene therapy to get the same result seems unlikely, said Dominguez-Bendala, an associate professor at the University of Miami's Diabetes Research Institute.

"I don't see something like this coming to the clinic for diabetes," he said.

But Dominguez-Bendala also pointed to what's "cool" about the experiments.

Wu's team used a recently developed technology called CRISPR (pronounced "crisper") to create the skin patches. The technique, heralded as a major breakthrough in genetic engineering, allows scientists to make precision "edits" in DNA -- such as clipping a particular defect or inserting a gene at a specific location.

Before CRISPR, scientists could not control where an inserted gene would be integrated into the genome. It might end up in a "bad" location, Dominguez-Bendala explained, where it could, for example, "awaken" a tumor-promoting gene.

Wu and colleauges used CRISPR to make specific edits in GLP1, including one that allowed the gene to be turned "on" or "off" as needed, by using the antibiotic doxycycline.

The modified gene was inserted into mouse stem cells, which were then cultured into skin grafts in the lab. Finally, those grafts were transplanted onto lab mice.

The researchers found that when the mice were fed food with tiny amounts of doxycycline, the transplanted skin released GLP1 into the bloodstream. In turn, the animals' insulin levels rose and their blood sugar dipped.

The engineered skin also seemed to protect the mice from the ravages of a high-fat diet. When the mice were fed a fat-laden diet, along with doxycycline, they gained less weight versus normal mice given the same diet. They also showed less resistance to the effects of insulin, and lower blood sugar levels.

According to Wu, the study lays the groundwork for more research into using skin cells as a way to deliver "therapeutic proteins."

For instance, he said, skin cells could be engineered to provide an essential protein that is missing because of a genetic defect. As an example, he cited hemophilia -- a genetic disorder in which people lack a protein that allows the blood to clot properly.

Skin cells could be an ideal way to deliver such therapies, Wu said.

For one, the safety of skin grafts in humans is well-established, he pointed out. Since the 1970s, doctors have known how to harvest skin stem cells from burn victims, then use those cells to create lab-grown skin tissue.

Because the skin is generated from a patient's own stem cells, that minimizes the issue of an immune system attack on the tissue.

Dominguez-Bendala agreed that using skin cells has advantages. For one, he noted, the skin graft can be easily removed if something goes awry.

But a lot of work remains before therapeutic skin grafts could become a reality for any human disease. And research in animals doesn't always pan out in humans.

A next step, Wu said, is to see whether the skin grafts maintain their effects in lab mice over a longer period. The researchers will also monitor the animals for any immune system reactions against the GLP1 protein itself.

The findings were published online Aug. 3 in Cell Stem Cell.

The U.S. National Institutes of Health has a primer on gene therapy.

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Engineered Skin Cells Control Type 2 Diabetes in Mice: Study - Arizona Daily Star

Skin Stem Cells Comments Off on Engineered Skin Cells Control Type 2 Diabetes in Mice: Study – Arizona Daily Star | August 4th, 2017

We lost an American icon Thursday with the death of actor and playwright Sam Shepard. He had ALS (amyotrophic lateral sclerosis), more commonly known in the U.S. as Lou Gehrigs disease. Its an invariably fatal neurological disease that robs individuals of their ability to move muscles, their ability to swallow, and eventually, their ability to breathe.

ALS often starts in a fairly nonspecific way, with weakness in a persons hand or foot. Although I never examined the late Mr. Shepard, even in public photos from 2016, the atrophy of his hand muscle was evidenta hallmark of the loss of muscle that occurs in ALS.

In about 90% of cases diagnosed by neurologists, ALS happens out of the blueits sporadic, and the cause isnt known. About 10% of the time, ALS is inherited through a defective gene; that is, a patient has a family member who also had the disease. We can readily diagnose inherited ALS with a relatively simple blood test.

Five years ago, we learned that even in some patients who have no family history of ALS, a defect in a gene known as C9orf72 underlies the disease. In some patients, the disease may be initially diagnosed incorrectly as a nerve problem in the hands or wrist (carpel tunnel syndrome), or a pinched nerve in the neck or back. But those conditions are commonly associated with painALS is not generally a painful disease.

The weakness typically progressesslowly over many years in some patients, or rapidly over a few months in othersprogressing from one hand to the other, from hand to foot, or foot to hand. Eventually it affects ones ability to chew, swallow, and breathe. The weakness of the breathing muscles is what makes ALS fatal. Unlike cancer, with its rare but real remissions, ALS is always fatal. Patients might choose to have a ventilator artificially breathe for them; that intervention delays death, but not the progressive weakening and paralysis of all muscles.

As treating physicians, we have a paucity of options to slow down the disease and have no real effective drug to halt its relentless progression or to recover functionno cure. ALS is not really one disease, but a combination of different genetic, even environmental, insults, that culminate in this horribly disabling and life-ending malady. Not unlike what we have learned about cancers, there may be many different causesgenetic, molecular, biochemicalthat underlie the disease. In cancers, sampling the actual diseased tissue, commonly through tissue biopsies, has provided a trove of clues about what underlies the basis of the different cancers and how to approach the different forms, sometimes quite successfully. But with ALS, we cannot readily take a chunk of someones brain or spinal cord, so we are often left guessing as to what may underlie the cause of the disease and how to best treat it. That antiquated approach may soon end.

Advances in the generation of stems cells from individual patients provide the most powerful way to generate their own brain cells. We are now able to take a small tube of blood or skin and turn those cells into stem cells (by a procedure that won the Noble prize several years ago), and then, by adding a few more chemicals and special genes, turn those cells into motor neuronsbrain and spinal cord cells that die in ALS.

This procedure, which in essence creates a biopsy of the brain/spinal cord of ALS patients, will allow us to achieve what has been so successful in cancerto truly understand the different kinds of ALS, to use our patients brain cells to discover their individual disease causes, and to develop a more individualized pathway for drug therapy. We aim to personalize ALS therapywhat we call Answer ALS. That is the hope on the horizon for ALS, along with drugs now already under development or in clinical trials that are specifically targeted to patients with known genetic mutations. How far that horizon is in the distance, we dont know, but we can see it. We only wish Mr. Shepard and all our past patients could have reached that hopeful horizon.

Jeffrey D. Rothstein MD, PhD, a neurologist and professor at Johns Hopkins University, is the director of the universitys Brain Science Institute, ALS clinic and Robert Packard Center for ALS Research.

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Sam Shepard Died of ALS. Here's Why It's so Difficult to Treat. - Fortune

Skin Stem Cells Comments Off on Sam Shepard Died of ALS. Here’s Why It’s so Difficult to Treat. – Fortune | August 2nd, 2017

By Jacqueline Howard CNN

(CNN) -- Scientists are getting one step closer to snipping inherited genetic diseases out of human offspring using a gene-editing technique called CRISPR.

For the first time, scientists said, they corrected a gene mutation linked to inherited heart conditions in human embryos using the approach. A study demonstrating the technique was published in the journal Nature on Wednesday (PDF).

Last week, the MIT Technology Review released the first news of this scientific feat, describing the research as the first-known attempt at creating genetically modified human embryos in the United States.

However, Juan Carlos Izpisua Belmonte, a co-author of the study, described it as the first in the world to demonstrate gene-editing to be safe, accurate and efficient in correcting a pathogenic gene mutation in human embryos. Previous attempts by Chinese researchers were unsuccessful at achieving this without safety concerns.

"This is the first that has been demonstrated as safe and working," said Belmonte, a professor at the Salk Institute for Biological Studies' gene expression laboratory in La Jolla, California.

"All cells of the embryo were corrected," he said. "It seems to be working from these samples that we have chosen, but we need to do much more basic research with many other genes."

The study was a collaboration between the Salk Institute, the Oregon Health & Science University in Portland and Korea's Institute for Basic Science.

Scientists estimate that more than 10,000 human diseases may result from mutations to a single gene occurring in all cells of the body, according to the World Health Organization.

Cutting and correcting gene mutations

The study used 75 human zygotes in which the father carried a mutation on the MYBPC3 gene, Belmonte said. The eggs used to produce the zygotes did not carry that gene mutation. The researchers noted that they received informed consent from the donors of the eggs, sperm and embryos used in the study.

The goal was to correct a type of inherited heart condition. A mutation called MYBPC3 is associated with inherited heart conditions, including left ventricular noncompaction, familial dilated cardiomyopathy and familial hypertrophic cardiomyopathy, which affects an estimated one in 500 people worldwide.

Hypertrophic cardiomyopathy also is thought to be the most common inherited or genetic heart disease in the US, according to the Centers for Disease Control and Prevention.

In a lab dish, the researchers used CRISPR, a gene-editing technique, to remove the harmful MYBPC3 mutation from the human zygotes. Then, the zygotes' own DNA-repair mechanism replaced what was cut out with a copy of a MYBPC3 gene from the mother, which did not carry a mutation, Belmonte said.

"A male research subject known to be heterozygous for this gene mutation was recruited for the study, as were several healthy young egg donors," Dr. Paula Amato, an obstetrician-gynecologist at Oregon Health & Science University, said Tuesday. She was a co-author of the study.

"CRISPR was introduced at the time of sperm injection," she said. "Then, DNA repair of the embryos was assessed."

The researchers found that about 72% of zygotes were properly and safely corrected on the MYBPC3 gene, Belmonte said.

This method significantly differed from studies in which scientists used the CRISPR tool to manually replace what was cut out with whatever the scientists desired.

Researchers in China were the first to reveal attempts to modify genes in human embryos using CRISPR. Three separate studies were published in scientific journals describing Chinese experiments on gene editing in human embryos.

"The previous human studies done in China had very small numbers, and one of them used abnormal embryos," Amato said. "So we think this is the first, largest study from which you could draw some reasonable conclusions."

Some gene-editing attempts in human embryos have been problematic, resulting in an issue called mosaicism, in which the corrections made in one gene failed to replicate once that cell divided into two cells, those two cells divided into four cells and so on.

"So when the baby is born, all the cells do not have the mutation anymore. ... This study, it shows that we can correct the embryo and then, after the division, all the cells are corrected, so there's not what we call mosaicism," said Belmonte, who is also a member of the National Academies of Sciences, Engineering and Medicine's committee on human gene editing.

This year, the academies published a report on human genome editing that addressed potential applications of the technology, including the possible prevention or treatment of inherited diseases or conditions.

The future of gene editing

Though the researchers have expressed enthusiasm around their new study, they also noted that the findings must be replicated in followup research before this gene-editing approach can move forward to clinical trials.

"The fact that it is, apparently, a new and poorly understood mechanism and it is not the now standard CRISPR 'cut and replace' method adds to the time needed for research into its safety and effectiveness," said Hank Greely, professor of law and genetics at Stanford University, who was not involved in the new study.

Yet future research can come with some political challenges, Amato said.

"First of all, there are regulations regarding use of federal funds for embryo research, so the (US National Institutes of Health) does not currently support embryo research, so that's one barrier. The other barrier is, the (US Food and Drug Administration) is prohibited from considering any clinical trials related to germline genetic modification," she said.

In this new study the embryos were only allowed to mature to day three after fertilization before they were disaggregated, or isolated into various components, for further analysis.

In the far-off future, a clinical trial could include transplanting corrected embryos into a uterus with the goal of establishing pregnancy and then monitoring the embryos as they develop into children.

Still, "it is way too early to contemplate implanting the edited embryos for the purpose of actually establishing a pregnancy," said Dana Carroll, a professor of biochemistry at the University of Utah who was not involved in the new study but has used CRISPR in his own research.

"The genome editing tools are currently not sufficiently efficient and specific to be reliable, and regulatory and oversight processes have not been established," Carroll said, adding that the work on the new study was "well-done" and "well-presented."

"The authors have made an important discovery regarding the repair of CRISPR-induced DNA breaks in human eggs just at the time of fertilization," he said.

"This information will help to guide ongoing research, and it demonstrates that research on early-stage human embryos will be necessary to establish safe and effective procedures in the long run," he said. "There is still a lot of work to do to understand repair processes in very early embryos and to optimize the use of the CRISPR reagents, but this study makes a valuable contribution."

Some CRISPR critics have argued that gene editing may give way to eugenics and to allowing embryos to be edited with certain features in order to develop so-called designer babies.

However, the researchers wrote in their study that they hope CRISPR could be considered as an alternative option to preimplantation genetic diagnosis, also known as PGD, for couples at risk of passing on an inherited disease.

'This opens up the possibility for those embryos'

PGD, developed about a quarter-century ago, is a genetic testing procedure typically conducted after in vitro fertilization to diagnose a genetic disease or condition in an embryo before it is implanted.

Since the human genome contains two copies of each gene -- paternal and maternal alleles, or variant forms of genes -- a mutation affecting only one allele is called heterozygous.

When only one parent carries a heterozygous mutation on a gene, about half of the embryos from that parent should be mutation-free while the others would have the mutation. Selectively, the parents' doctor would chose the healthy embryos to be implanted and discard the embryos with the mutations, Belmonte said.

Sometimes, "a couple that wants to have a baby and they have a mutation, they may not have enough embryos to choose from," he said. This is when CRISPR can come in.

"This technology, independent of the embryos that are there, it would go on and correct all of them. ... This opens up the possibility for those embryos," he said. "That's important because after the first implantation, if it doesn't work, you can do it again."

The researchers wrote in their study, "PGD may be a viable option for heterozygous couples at risk of producing affected offspring. In cases when only one parent carries a heterozygous mutation, 50% of embryos should be mutant. In contrast, targeted gene correction can potentially rescue a substantial portion of mutant human embryos, thus increasing the number of embryos available for transfer."

Nonetheless, using CRISPR in that way remains a long way off.

Shoukhrat Mitalipov, director of the Oregon Health & Science University's Center for Embryonic Cell and Gene Therapy, helped lead the new study. In 2013, Mitalipov and his colleagues reported the first success in cloning human stem cells, reprogramming human skin cells back to their embryonic state. In 2007, a research team led by Mitalipov announced that they created the first cloned monkey embryo and extracted stem cells from it.

Now, when it comes to using CRISPR to correct gene mutations in embryos, Mitalipov said Tuesday, "We've done some ground work. ... There is still a long road ahead, and it's unclear at this point when we will be allowed to move on."

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Scientists edit disease-causing gene mutation in human embryos - WENY-TV

Skin Stem Cells Comments Off on Scientists edit disease-causing gene mutation in human embryos – WENY-TV | August 2nd, 2017

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Random differences between cells early in development could be the key to making different cells in the body, according to new research from a team co-led by Professor Wolf Reik. Different cell types - brain, blood, skin, gut etc. - all have unique and vital roles, yet they all start out the same. Cells become different as a result of a long sequence of biochemical choices made before we're born. For us to be healthy, these choices need to ensure we get the right number of each cell type.

Scientists at the Babraham Institute, EMBL-EBI and the Wellcome Trust-Medical Research Council Stem Cell Institute examined the genetics of stem cells from embryos at the earliest stages of development. Typically, cells of the same type have matching patterns of gene activity - many of the same genes are turned off or on in all cells. This latest research, published in the journal Cell Reports reveals that when cells start specialising into different cell types their gene activity becomes more 'noisy' - each cell starts to turn different groups of genes on or off.

The results, which focus on two choices near the start of embryo formation, show that, when cells are making decisions about what to become, there is greater variation in the activity of the genes in different cells - the same genes may be turned on in some cells and off in others. By chance this noise will make some cells more likely to become one type of cell, whilst others will start to favour an alternative.

The paper's co-first authors were Hisham Mohammed, Irene Hernando-Herraez and Aurora Savino. Dr Mohammed at the Babraham Institute, said: "Our analyses suggest that elevated transcriptional noise at two key points in early development coincides with cell fate decisions. By contrast, after these decisions cells become highly synchronised and grow rapidly. Our study systematically charts transcriptional noise and uncovers new processes associated with early lineage decisions."

This process of making similar cells become different is called symmetry breaking. This study marks the first time that a technique called single-cell sequencing has been used to examine individual cells from mouse embryos in the early stages of development. Previous research has only examined groups of cells, so it has been impossible to investigate the differences between cells during symmetry breaking.

Co-senior author Professor Jennifer Nichols at the Wellcome Trust-Medical Research Council Stem Cell Institute, said: "Our data allow us to study gene activity in individual cells to an unprecedented level of precision. This detail has allowed us to observe substantial differences between cells. Regulating noisy gene activity during development may be a key part of how cells make decisions about their future. In the future we hope to discover how this process is controlled to better understand how noise shapes early development."

As the lead computational scientist on the paper, Dr John Marioni at EMBL-EBI, said: "Making sense of the data generated in studies like this is only possible thanks to ongoing advances in computational biology. With more than 10,000 pieces of data being collected about each individual cell, modern computers are essential in achieving the level of sensitivity needed for this type of research."

Explore further: Controlling gene activity in human development

More information: Cell Reports (2017). DOI: 10.1016/j.celrep.2017.07.009

Journal reference: Cell Reports

Provided by: Babraham Institute

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Noise helps cells make decisions: Team reveals the importance of genetic noise in development - Phys.Org

Skin Stem Cells Comments Off on Noise helps cells make decisions: Team reveals the importance of genetic noise in development – Phys.Org | August 1st, 2017

Kristin Comella, Chief Science Officer

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, and is projected to be the third by 2020. COPD is associated with an exaggerated chronic inflammatory response causing airway abnormalities. Patients typically undergo a progression of declining lung function, characterized by an increase of cough, shortness of breath, and mucus production. Extra-pulmonary manifestations of COPD include osteoporosis, cardiovascular disease, skeletal muscle abnormalities, and depression. There is currently no cure and the manifestations can only be treated symptomatically. It afflicts more than 5% of the population in many countries and accounts for more than 600 billion in health care costs, morbidity, and mortality.

Adult stem cells are found in every part of the body and their primary role is to heal and maintain the tissue in which they reside. Stem cells are unspecialized cells capable of renewing themselves by cell division. In addition, they have the ability to differentiate into specialized cell types. Adult stem cells can be harvested from a patients own tissue, such as adipose (fat) tissue, muscle, teeth, skin or bone marrow. One of the most plentiful sources of stem cells in the body is the fat tissue. In fact, approximately 500 times more stem cells can be obtained from fat than bone marrow. Stem cells derived from a patients own fat are referred to as adipose-derived stem cells (ADSCs). Adipose derived stem cells have been explored with respect to their activity in diseases involving significant inflammatory or degenerative components. More recently, adult stem cells have been identified as having the potential to reverse the effects of diseases like COPD.

The mixed population of cells that can be obtained from fat is called a stromal vascular fraction (SVF). The SVF can easily be isolated from fat tissue in approximately 30-90 minutes in a clinic setting (under local anesthesia) using a mini-lipoaspirate technique. The SVF contains all cellular elements of fat, excluding adipocytes. Tens to hundreds of millions of ADSCs can be obtained in the context of the SVF acquired from 20-200 ml of adipose tissue during this out-patient procedure. This sets the stage for their practical use at the point-of-care, in which a preparation of ASC can be provided for infusion or injection after the mini-liposuction. COPD patients who have undergone stem cell therapies often express the willingness to receive additional cell infusions if possible, due to a feeling of well-being associated with the injection. There is early evidence of feasibility and safety of infusions into the patients with COPD. In relevant studies, intravenous infusion of cultured adipose stem cells has been demonstrated to remarkably improve the onset and progression of smoke exposure-induced emphysema in rodents.

Stem cells possess enormous regenerative potential. The potential applications are virtually limitless. Patients can receive cutting edge treatments that are safe, compliant, and effective. Our team has successfully treated over 7000 patients with very few safety concerns reported. One day, stem cell treatments will be the gold standard of care for the treatment of most degenerative diseases. We are extremely encouraged by the positive patient results we are seeing from our physician-based treatments. Our hope is that stem cell therapy will provide relief and an improved quality of life for many patients. The future of medicine is here!

For additional information on Stem Cell Centers of Excellences South Miami clinic, visit http://www.stemcellcoe.com.

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Stem Cells Offer New Solutions for Lung Disease - Miami's Community Newspapers

Skin Stem Cells Comments Off on Stem Cells Offer New Solutions for Lung Disease – Miami’s Community Newspapers | August 1st, 2017

Malfunctioning glial cells that keep nerve cells from forming working communication networks may be the basis of the wiring problems in the brains of people with schizophrenia, new research suggests.

The inability of these cells to do their jobappears to be a primary contributor to the disease.

When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia into mice, the animals nerve cell networks did not mature properly and the mice exhibited the same antisocial and anxious behaviors seen in people with the disease.

The findings of this study argue that glial cell dysfunction may be the basis of childhood-onset schizophrenia, says neurologist Steve Goldman, co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study.

The inability of these cells to do their job, which is to help nerve cells build and maintain healthy and effective communication networks, appears to be a primary contributor to the disease.

Glia are an important family of support cells found in the brain and play a critical role in the development and maintenance of the brains complex interconnected network of neurons. Glia includes two major types: astrocytes and oligodendrocytes.

Astrocytes are the brains principal support cells, while oligodendrocytes are responsible for producing myelin, the fatty tissue that, like the insulation on electrical wires, wraps the axons that connect different nerve cells. The source of both these cells is another cell type called the glial progenitor cell (GPC).

Astrocytes perform several functions in the brain. During development, astrocytes colonize areas of the brain and establish domains in which these cells help direct and organize the network of connections between nerve cells.

Individual astrocytes also send out hundreds of long fibers that interact with synapsesthe junction where one neurons axon meets anothers dendrite. The astrocytes help facilitate the communication between neurons at the synapses by regulating the flow of glutamate and potassium, which enable neurons to fire when they are communicating with each other.

In the new study, the researchers obtained skin cells from individuals with childhood-onset schizophrenia and reprogrammed the cells to create induced pluripotent stem cells (iPSC) which, like embryonic stem cells, are capable of giving rise to any cell type found in the body. Next, the team manipulated the iPSCs to create human GPCs.

The human GPCs were then transplanted into the brains of neonatal mice. These cells out-competed the animals own native glia, resulting in mice with brains comprised of animal neurons and human GPCs, oligodendrocytes, and astrocytes.

The researchers observed that human glial cells derived from schizophrenic patients were highly dysfunctional. The development of oligodendrocytes was delayed and the cells did not create enough myelin-producing cells, meaning signal transmission between the neurons was impaired.

The development of astrocytes was similarly tardy so that the cells were not present when needed and were thus ineffective in guiding the formation of connections between neurons. The astrocytes also did not mature properly, resulting in misshapen cells that could not fully support the signaling functions of the neurons around them.

The astrocytes didnt fully mature and their fibers did not fill out their normal domains, meaning that while they provided control to some synapses, others had no coverage, says Martha Windrem, also with the Center for Translational Neuromedicine and first author of the study. As a result, the neural networks in the animals became desynchronized and uncoordinated.

The researchers also subjected the mice to a series of behavioral tests. They observed that the mice with human glial cells from individuals diagnosed with schizophrenia were more fearful, anxious, anti-social, and had a variety of cognitive deficits compared to mice transplanted with human glial cells obtained from healthy people.

The studys authors point out that the new research provides scientists with a foundation to explore new treatments for the disease. Because schizophrenia is a unique to humans, until now scientists have been limited in their ability to study the disease. The new animal model developed the by the researchers can be used to accelerate the process of testing drugs and other therapies in schizophrenia.

The study also identifies a number of glial gene expression flaws that appear to create chemical imbalances that disrupt communication between neurons. These abnormalities could represent targets for new therapies.

Additional coauthors of the study are from the University of Rochester, the University of Copenhagen, George Washington University, Johns Hopkins University, and Case Western University.

The study appears in the journal Cell. Funding from National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the G. Harold and Leila Y. Mathers Charitable Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the Novo Nordisk and Lundbeck Foundations supported the research.

Source: University of Rochester

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Glial cells botch wiring in childhood schizophrenia - Futurity: Research News

Skin Stem Cells Comments Off on Glial cells botch wiring in childhood schizophrenia – Futurity: Research News | July 31st, 2017

Over the past twenty years, Jamie Sherrill has become one of the most in-demand skincare gurus in Hollywood. But you may not know her name--she goes by the moniker Nurse Jamie, which is also the name of her line of cult-favorite beauty tools and potions, as well as her Los Angeles spa, Nurse Jamie Beauty Park. Before you ask--yes, Sherrill is, in fact, a nurse, but she's also a certified aesthetician, which means she can offer her devoted clients, who range from Jessica Alba to Ruby Rose, a wide-range of services that promise flawless skincare through some very unique methods that can be done both at home and in the office. "At Nurse Jamie Beauty Park, our vision is simple to offer not only the best non-surgical beauty solutions available on the market, but also a customized combination of the most cutting-edge technical advances in anti-aging, skincare and beauty today," Sherrill explains. "High-tech tools, devices and home-based care are a big part of my regiment and I make everyone participate."

Here, Sherrill offers insight into the most in-demand celebrity beauty desires, and offers tips on improving your complexion at home.

You have a wide range of high profile clients, all unique with their own concerns and skincare regimens. What are the most common concerns you hear?Celebrities come in all shapes, sizes and ages, so everyone is going to have a different treatment plan. This year body sculpting is big from banning the bra strap fat to firming the tush, while laser hair removal, Botox, fillers and glowing skin are year round trends. Those requests never go out of style.

What types of treatments are most requested before a red carpet appearance?Some are genetically blessed and don't really do more than an oxygen facial and an electric facial"to be fully red carpet ready. But that said--we start to lose collagen production and skin elasticity starting at 25, so we will typically use a range of key technologies in lasers for skin texture and complexion.TheACELLeratorat home beauty tool is idealto help serums and product be absorbed for a lifting and tightening effect, and has a great anti-inflammatory property. You can use every day but specifically just before an event for a more open eye look or more defined cheek even if you just flew in!This works well for the face and body, so it helps with stretch marks and skin smoothing for waistline, hips and thighs. Trust me this is acelebsecret. If you don't believe me, do one side of your face for just one minute then look into a mirror.

But don't forget red carpet prep needs to happen every day, too. Eat well, sleep well on the right pillow, take off make-up at night and use good quality products with the best raw ingredients. Home care matters as much as in office does.

When your clients are on location for months at a time, what tips do you give them?Think maintain, not reclaim and always try to be preventative.Think of the rules of eating that are good for your body; most apply to your skin as well. It is the largest organ of the body so treat it like one.Be consistent with taking off makeup nightly and never with a washcloth. Use a hypoallergenic and antibacterial surface to cleanse your skin. Exfoliate regularly, manually or with a tool, but gently and consistently.

Invest in a beautytool to help increase absorption of products like my Instant Uplift or ACELLerator Ultra. Just like the machines we have in office, they increase absorption and efficacy of your products while helping to improve and maintain tone. Also, wear sunscreen.It seems basic, but all helps. At-home devices are the future of beauty -- you can have the best raw ingredients in the world, but as skin is the largest organ of the body its main function is to protect. The number one cause of aging is UV damage, the number two is smoking, and the third is sleeping on a traditional pillow.Use satin only and a shape that will help you train to sleep on your back, so that the most delicate areas around the eyes, cheeks and neck do not form permanent wrinkles.

It's the middle of summer. Other than sunscreen and hats, what other advice do you have for fending off skin discoloration?Use good quality products with the best raw ingredients. Old school skincare was to use aggressive products that caused chemical cell turnover reaction, which can make you more susceptible to sun damage. (Retin-A is so 1980s!) My opinion is to use retinol ingredients sparingly. Epidermal Growth Factor (EGF) - causes cell turnover and has significant effects on delaying the aging process - including preserving skins cells and skins overall vitality and radiance, without leaving you red, flaky, and shiny. I hate the shiny face -it kills meovertime I see I can spot theglare from across the room.The Nurse Jamie tools that you incorporate into your treatments seem to have a loyal following of their own. Like the Beauty Stamp, for example. How does that work?The Beauty Stamp may very well be the best investment anyone can make. A small pad features a cross section of micro needles in a grid that helps with micro exfoliation, opens channels for product delivery and efficacy and aids in the body process of collagen andelastinproduction. It is my triple threat. For day of events you need to focus on complexion and texture in a non-invasive way or only protocols with no downtime and no risk. Don't try something new with a high risk to low reward for the day of an event. Nothing worse than redness or inflammation when you are dressed to impress and need your face to match! How about the Accelerator Ultra?TheACELLeratorat home beauty tool is ideal for a daily regimentto help serums and product be absorb lifting and tightening effect and has a great anti-inflammatory property.You can use every day but specifically just before an event for a more open eye look or more defined cheek--even if you just flew in! This works well for face and body so it helps with stretch marks and skin smoothing for waistline, hips and thighs, too. Trust me, this is acelebsecret dont believe me? Do one side of your face for just one minute then look into a mirror.What is your top selling tool?UpLift Massaging Beauty Roller. It has a huge celebrity following.Are there any foods or vitamins that you recommend for vibrant skin?A B12 Energy Shot. Close to a decade ago I injected Paris Hilton and Nicole Richie with it right in their bums on national television forThe Simple Life,and in turn injectable vitamins became one of our most popular treatments...

What are the biggest skincare mistakes people make?Side sleeping and over exfoliating. We need to treat our skin like a silk fabric not a piece of leather. When youoverexfoliate(physically and chemically) and withtoo much frequency it destroys the protective barrier that your skin has - once it is removed or compromised you are you exposing your skin to environmental toxins, sun damage pre-mature aging, acne, etc. It's very common.

What is your personal daily skin routine?Taking off my make-up--I can't go to bed with my make-up on. Period. The UpLift Facial Massaging Beauty Roller, EGF Stem Cell Complex--I dont go anywhere without this cream. I would bathe in it if I could--and I use my ACELLerator for 10 minutes each night on both sides of my face while I sit in bed.I practice what I preach.That way I can give them my best face - and tell them it is what I do and mean it! Ive dedicated my life to skin and created my line for products that I felt that were missing in the marketplace. As a busy working mom of three toddlers Im proud to say that Im my own client.

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Celebrity Skincare Guru Nurse Jamie on Why At-Home Beauty Tools Are the Future - W Magazine

Skin Stem Cells Comments Off on Celebrity Skincare Guru Nurse Jamie on Why At-Home Beauty Tools Are the Future – W Magazine | July 31st, 2017

Investigators from Brigham and Womens Hospital (BWH) and the Harvard Stem Cell Institute (HSCI) may have discovered a way to kill tumor cells that have metastasized to the brain.

The team has developed cancer-killing viruses that can deliver stem cells via the carotid artery, and applied them to metastatic tumors in the brains of clinically relevant mouse models. The elimination of metastatic skin cancer cells from the brains of these preclinical models resulted in prolonged survival, the investigators report. The study, published online this week in the journal PNAS, also describes a strategy of combining this therapy with immune checkpoint inhibitors.

Metastatic brain tumors often from lung, breast, or skin cancers are the most commonly observed tumors within the brain and account for about 40 percent of advanced melanoma metastases. Current therapeutic options for such patients are limited, particularly when there are many metastases, said Khalid Shah, director of the Center for Stem Cell Therapeutics and Imaging (CSTI) in the BWH Department of Neurosurgery, who led the study. Our results are the first to provide insight into ways of targeting multiple brain metastatic deposits with stem-cell-loaded oncolytic viruses that specifically kill dividing tumor cells.

In their search for novel, tumor-specific therapies that could target multiple metastases in the brain without damaging adjacent tissues, the research team first developed different BRAF wild-type and mutant mouse models that more closely mimicked what is seen in patients.

They found that injecting patient-derived, brain-seeking melanoma cells into the carotid arteries of the preclinical models resulted in metastatic tumors forming throughout the brain, mimicking what is seen in advanced melanoma cancer patients. The injected cells express markers that allow them to enter the brain and are labeled with bioluminescent and fluorescent markers to enable tracking by imaging technologies.

To devise a potential new therapy, the investigators engineered a population of bone marrow-derived mesenchymal stem cells loaded with oncolytic herpes simplex virus (oHSV), which specifically kills dividing cancer cells while sparing normal cells.

Previous research by Shah and his colleagues had shown that different stem cell types were naturally attracted to tumors in the brain. After first verifying that stem cells injected to the brain would travel to multiple metastatic sites and not to tumor-free areas in their model, the team injected the oHSV-laden stem cells into the carotid arteries of metastasis-bearing mice. This led to significantly slower tumor growth and increased survival, compared with the models that received unaltered stem cells or control injections.

Shah and his colleagues also developed an immunocompetent melanoma mouse model and explored treatments with both stem cell-loaded oHSV and immune checkpoint blockers such as those that target the PD-1/PD-L1 pathway. They found that PD-L1 immune checkpoint blockade significantly improved the therapeutic efficacy of stem cell-based oncolytic virotherapy in melanoma brain metastasis.

We are currently developing similar animal models of brain metastasis from other cancer types, as well as new oncolytic viruses that have the ability to specifically kill a wide variety of resistant tumor cells, said Shah, who is also a professor at Harvard Medical School and a principal faculty member at the Harvard Stem Cell Institute. We are hopeful that our findings will overcome problems associated with current clinical procedures. This work will have direct implications for designing clinical trials using oncolytic viruses for metastatic tumors in the brain.

The study was supported by a Department of Defense Idea Award and a grant from the National Institutes of Health.

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New approach may kill tumor cells in the brain - Harvard Gazette

Skin Stem Cells Comments Off on New approach may kill tumor cells in the brain – Harvard Gazette | July 12th, 2017

According to recent study, advancements in materials from this study could potentially help patients requiring stem cell therapies for spinal cord injuries, stroke, Parkinsons disease, Alzheimers disease, arthritic joints or any other condition requiring tissue regeneration. Earlier research revolved around the role of autoimmunity in terms of a treatment.

Its important in the context of cell therapies for people to cure these diseases or regenerate tissues that are no longer functional, shared Samuel I. Stupp, director of Northwesterns Simpson Querrey Institute for BioNanotechnology and Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering.

Cells in our bodies are constantly being signalled with many types of instructions coming from proteins and other molecules present in the matrices that surround them. For example, these can be cues for cells to express specific genes so they can proliferate or differentiate into several types of cells leading to growth or regeneration of tissues. One of the marvels of this signalling machinery is the built-in capacity in living organisms to make signals stop and restart as needed, or to switch off one signal and activate a different one to orchestrate very complex processes.

The new technology manipulates cells by converting the skin cells to cure a patient with Parkinsons disease. (Shutterstock)

Building artificial materials with this type of dynamic capacity for regenerative therapies has been virtually impossible so far. The new work published today reports the development of the first synthetic material that has the capability to trigger reversibly this type of dynamic signalling. The platform could not only lead to materials that manage stem cells for more effective regenerative therapies, but will also allow scientists to explore and discover in the laboratory new ways to control the fate of cells and their functions.

One of the findings is the possibility of using the synthetic material to signal neural stem cells to proliferate, then at a specific time selected by the operator, trigger their differentiation into neurons and then return the stem cells back to a proliferative state on demand. The paper also reports that spinal cord neural stem cells, initially grouped into structures known as neurospheres, can be driven to spread out and differentiate using a signal.

But when this signal is switched off, the cells spontaneously regroup themselves into colonies. This uncovers strong interactions among these cells that could be important in understanding developmental and regenerative cues. The potential use of the new technology to manipulate cells could help cure a patient with Parkinsons disease. The patients own skin cells could be converted to stem cells using existing techniques.

The new technology could help expand the newly converted stem cells in vitro in the lab and then drive their differentiation into dopamine-producing neurons before transplantation back to the patient. In the new technology, materials are chemically decorated with different strands of DNA, each designed to display a different signal to cells.

People would love to have cell therapies that utilize stem cells derived from their own bodies to regenerate tissue. In principle, this will eventually be possible, but one needs procedures that are effective at expanding and differentiating cells in order to do so. Our technology does that, noted Stupp. While this process is currently only done in vitro with the vision of then transplanting cells, Stupp said in the future it might be possible to perform this process in vivo.

The stem cells would be implanted in the clinic, encapsulated in the type of material described in the new work, via an injection and targeted to a particular spot. Then the soluble molecules would be given to the patient to manipulate proliferation and differentiation of transplanted cells. The study was published in journal Nature Communications.

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Cells may hold key to treating Parkinson's disease - Hindustan Times

Skin Stem Cells Comments Off on Cells may hold key to treating Parkinson’s disease – Hindustan Times | July 12th, 2017

Those who know ancient historythe first decade of the 21st centuryrecall that embryonic stem cell research was a combustible issue, with supporters cheering the potential to create new tissues from stem cells and opponents decrying the destruction of human embryos that it required. A breakthrough arrived in 2006, when a Japanese researcher developed induced pluripotent stem cells (iPS), adult cells that behaved like embryonic stem cells and had an amazing ability to develop into muscles, skin, nerves, and almost any other cell type. Two years later, a second breakthrough, this one by Gustavo Mostoslavsky, a School of Medicine associate professor of gastroenterology, produced a tool that made it simpler and more efficient to generate iPS. BU patented his tool, called STEMCCA, and he says that its been adopted by more than 700 laboratories worldwide for making iPS.

That contribution to the field has earned Mostoslavsky this years University Innovator of the Year award. The Technology Developmentoffice presents the award to a faculty member whose research yields inventions or innovations benefiting society. Mostoslavsky will receive the award today at BUs annual Tech, Drugs, and Rock n Roll networking event connecting BU researchers and Boston entrepreneurs.

I was humbly surprised and happy, he says, when Gloria Waters, vice president and associate provost for research, emailed him the news. Sometimes it is easy to lose perspective when we get busy on the many tasks of running a labgrant writing, mentoring, budget, and so forthso I guess it is nice, once in a while, to just stop and enjoy the moment, enjoy what we have done so far, and even better, if on the way we have helped many others succeed.

One way Mostoslavsky has helped others succeedthe way that makes him most proud, he saysis to have cofounded, in 2010, BUs Center for Regenerative Medicine, which he codirects. The center, which pursues stem cell research with an emphasis on lung, blood, and gastrointestinal tract diseases, practices open source biology: sharing its discoveries with scientists around the world for free rather than patenting them. In 2013, CReM moved into its own physical quarters on Albany Street on the Medical Campus.

I am delighted to see Dr. Mostoslavskys colleagues choose him for this award, says Waters. STEMCCA has dramatically improved the efficiency with which new stem cells can be generated to treat disease. His success in patenting a tool that has become industry-standard, at the same time as he and the codirectors of the CReM have become renowned for their open source biology, serves as a model to students and other researchers of how to advance science through sharing, at the same time protecting important intellectual property.

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CReM Stem Cell Researcher Is Innovator of the Year - BU Today

Skin Stem Cells Comments Off on CReM Stem Cell Researcher Is Innovator of the Year – BU Today | July 12th, 2017

July 10, 2017 Credit: CC0 Public Domain

Investigators from Brigham and Women's Hospital (BWH) and the Harvard Stem Cell Institute have a potential solution for how to kill tumor cells that have metastasized to the brain. The team has developed cancer-killing viruses that can deliver stem cells via the carotid artery, and applied them to metastatic tumors in the brain of clinically relevant mouse models. The investigators report the elimination of metastatic skin cancer cells from the brain of these preclinical models, resulting in prolonged survival. The study, published online this week in the journal PNAS, also describes a strategy of combining this therapy with immune check point inhibitors.

"Metastatic brain tumors - often from lung, breast or skin cancers - are the most commonly observed tumors within the brain and account for about 40 percent of advanced melanoma metastases. Current therapeutic options for such patients are limited, particularly when there are many metastases," says Khalid Shah, MS, PhD, director of the Center for Stem Cell Therapeutics and Imaging (CSTI) in the BWH Department of Neurosurgery, who led the study. "Our results are the first to provide insight into ways of targeting multiple brain metastatic deposits with stem-cell-loaded oncolytic viruses that specifically kill dividing tumor cells."

In their search for novel, tumor-specific therapies that could target multiple brain metastases without damaging adjacent tissues, the research team first developed different BRAF wild type and mutant mouse models that more closely mimic what is seen in patients. They found that injecting patient-derived, brain-seeking melanoma cells into the carotid artery of these preclinical models resulted in the formation of many metastatic tumors throughout the brain, mimicking what is seen in advanced melanoma cancer patients. The injected cells express markers that allow them to enter the brain and are labelled with bioluminescent and fluorescent markers to enable tracking by imaging technologies.

To devise a potential new therapy, the investigators engineered a population of bone marrow derived mesenchymal stem cells loaded with oncolytic herpes simplex virus (oHSV), which specifically kills dividing cancer cells while sparing normal cells. Previous research by Shah and his colleagues shows that different stem cell types are naturally attracted toward tumors in the brain. After first verifying that stem cells injected to the brain would travel to multiple metastatic sites and not to tumor-free areas in their model, the team injected stem cells loaded with oHSV into the carotid artery of metastasis-bearing mice.. Injecting the stem cells loaded with oHSV into the carotid artery, a likely strategy for clinical application, led to significantly slower tumor growth and increased survival, compared with the models that received unaltered stem cells or control injections. The oHSV loaded stem cells are ultimately killed by oHSV mediated oncolysis, preventing the engineered cells from persisting within the brain, which is an important safety component in the therapeutic use of these stem cells.

Due to an increasing body of evidence which suggests that the host immune response may be critical to the efficacy of oncolytic virotherapy, Shah and his colleagues also developed an immunocompetent melanoma mouse model and explored treating with both stem cell loaded oHSV and immune checkpoint blockers such as the ones that target the PD-1/PD-L1 pathway. They found that PD-L1 immune checkpoint blockade significantly improved the therapeutic efficacy of stem cell based oncolytic virotherapy in melanoma brain metastasis.

"We are currently developing similar animal models of brain metastasis from other cancer types as well as new oncolytic viruses that have the ability to specifically kill a wide variety of resistant tumor cells," said Shah, who is also a professor at Harvard Medical School and a principal faculty member at the Harvard Stem Cell Institute. "We are hopeful that our findings will overcome problems associated with current clinical procedures. This work will have direct implications for designing clinical trials using oncolytic viruses for metastatic tumors in the brain."

Explore further: Stem-cell-based therapy promising for treatment of breast cancer metastases in the brain

More information: Wanlu Du el al., "In vivo imaging of the fate and therapeutic efficacy of stem cell-loaded oncolytic herpes simplex virus in advanced melanoma," PNAS (2017). http://www.pnas.org/cgi/doi/10.1073/pnas.1700363114

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Stem cell-based therapy for targeting skin-to-brain cancer - Medical Xpress

Skin Stem Cells Comments Off on Stem cell-based therapy for targeting skin-to-brain cancer – Medical Xpress | July 11th, 2017

Countries should unite to tackle unscrupulous advertising of unproven therapies involving stem cells, experts say.

An international group of leading experts has called for tighter regulation of so-called stem cell tourism. This involves patients travelling to other countries, where medical regulations are less strict, for treatment with potentially unsafe therapies.

Hundreds of medical centres around the world are offering therapies that involve transplantation of so-called stem cells -- which they claim have the ability to repair damaged tissues. Clinics are marketing the treatment for a range of conditions, including multiple sclerosis and Parkinson's disease.

Often these therapies are advertised directly to patients with the promise of a cure. But experts say there is often no evidence to show that the treatments will help anyone, or will not cause harm.

Researchers say the practice risks undermining the development of rigorously tested, validated therapies and puts lives at risk.

Writing in the journal Science Translational Medicine, the group has called for coordinated global action to tackle the problem.

They say tighter regulations on advertising stem cell therapies are needed, so that unsupported claims about potential clinical benefits do not go unchallenged.

Global regulatory authorities should agree international standards for the manufacture and testing of cell and tissue-based therapies, they add.

The group -- which includes experts from the University of Edinburgh -- also calls for the World Health Organization to help guide responsible clinical use of cells and tissues, as it does for medicines and medicinal devices.

Their appeal follows the deaths of two children at a clinic in Germany in 2010, which exploited a legal loophole to offer untested treatments. The clinic has since been closed.

Dr. Sarah Chan, a Chancellor's Fellow at the University of Edinburgh, said: "Many patients feel that potential cures are being held back by red tape and lengthy approval processes. Although this can be frustrating, these procedures are there to protect patients from undergoing needless treatments that could put their lives at risk.

"Stem cell therapies hold a lot of promise but we need rigorous clinical trials and regulatory processes to determine whether a proposed treatment is safe, effective and better than existing treatments."

Some types of stem cell transplantation - mainly blood and skin stem cells -- have been approved to treat certain types of cancer and to grow skin grafts for patients with severe burns. These treatments have been rigorously tested in clinical trials.

SOURCE: University of Edinburgh

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Medical Tourism in Spotlight as Experts Call for Tighter Regulation - Bioscience Technology

Skin Stem Cells Comments Off on Medical Tourism in Spotlight as Experts Call for Tighter Regulation – Bioscience Technology | July 11th, 2017