Archive for the ‘Skin Stem Cells’ Category

May 12, 2017

A new study from Lund University in Sweden shows that the behaviour of stem cells in plants and animals is surprisingly similar. The researchers were able to produce mathematical equations that reveal very small differences in the behaviour of the proteins. The results can hopefully be used in stem cell research involving humans.

"The plant and animal kingdoms were separated through evolution more than 1.6 billion years ago. It is surprising that the interactions between the handful of key genes that control the fate of each stem cell are so similar in both cases", says Carsten Peterson, professor at the Faculty of Science at Lund University.

Carsten Peterson is one of the researchers behind the recent study on differences and similarities between animal and plant stem cells. With a background in theoretical physics, he and his colleagues have tackled the stem cells from a different perspective, which proved successful.

By formulating mathematical equations, the researchers have performed a detailed study of the proteins that are central to the stem cells in mammals and plants. The proteins are linked to the genes that control the stem cells. In particular, the researchers have studied how these proteins mutually affect one another through interaction as the cells evolve.

"Although the proteins in mammalian and plant stem cells are very different when studied separately, there are major similarities in the ways in which they interact, that is, how they strengthen or weaken each other", says Carsten Peterson.

Stem cells are a hot topic in medical contexts, especially when it comes to cancer and autoimmune diseases. A stem cell is capable of evolving into several different types of cells and is thus a sort of mother cell to all of the body's specialised cell types. In animals, these specialised cells can never return to a stem cell state on their own. In plants, however, they can.

"Specialised cells of plants can return to being stem cells without external manipulation. In the plant world, there is a natural reprogramming process", says Carsten Peterson.

The mathematical equations show that very small differences are sufficient to explain why plant cells are so flexible while cells of mammals require artificial reprogramming to return to a stem cell state.

"When cells are influenced externally artificially for animals or naturally for plants the minor differences in interaction play a greater role, and the differences appear to be of greater significance", says Carsten Peterson.

He believes that a lot of work remains with regard to the efficiency of reprogramming of animal cells and therefore hopes that insights from the plant world can contribute. The current study provides clues about why it is so much easier to make a cell go back to being a stem cell in plants compared to mammals.

Reprogramming is a frequently used word in stem cell contexts today, ever since the Nobel Prize in Medicine and Physiology in 2012. One of the prize winners, Shinya Yamanaka, had demonstrated how to externally manipulate cells to return to an embryonic stem cell state by increasing the concentration of certain proteins. Turning back the clock this way has enormous potential in clinical contexts. For example, on an individual basis, skin cells can be reprogrammed into embryonic stem cells, and be made into desired cell types by manipulating certain proteins. This process is known as regenerative medicine.

The study was recently published in the scientific journal PLoS ONE.

Explore further: Study shows adipose stem cells may be the cell of choice for therapeutic applications

More information: Victor Olariu et al. Different reprogramming propensities in plants and mammals: Are small variations in the core network wirings responsible?, PLOS ONE (2017). DOI: 10.1371/journal.pone.0175251

Journal reference: PLoS ONE

Provided by: Lund University

An international team of researchers, funded by Morris Animal Foundation, has shown that adipose (fat) stem cells might be the preferred stem cell type for use in canine therapeutic applications, including orthopedic diseases ...

Freiburg plant biologist Prof. Dr. Thomas Laux and his research group have published an article in the journal Developmental Cell presenting initial findings on how shoot stem cells in plants form during embryogenesis, the ...

Scientists have discovered the gene essential for chemically reprogramming human amniotic stem cells into a more versatile state similar to embryonic stem cells, in research led by UCL and Heinrich Heine University.

A protein that stays attached on chromosomes during cell division plays a critical role in determining the type of cell that stem cells can become. The discovery, made by EPFL scientists, has significant implications for ...

Researchers from the Vavilov Institute of General Genetics, Research Institute of Physical Chemical Medicine and Moscow Institute of Physics and Technology (MIPT) have concluded that reprogramming does not create differences ...

Stem cells are typically thought to have the intrinsic ability to generate or replace specialized cells. However, a team of biologists at NYU showed that regenerating plants can naturally reconstitute their stem cells from ...

University of Dundee scientists have solved a mystery concerning one of the most fundamental processes in cell biology, in a new discovery that they hope may help to tackle cancer one day.

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A recent research paper in the Journal of Heredity reveals that there are three sub-species of snow leopard. Until now, researchers had assumed this species, Panthera uncia, was monotypic.

Adult stem cells have the ability to transform into many types of cells, but tracing the path individual stem cells follow as they mature and identifying the molecules that trigger these fateful decisions are difficult in ...

In their quest to replicate themselves, viruses have gotten awfully good at tricking human cells into pumping out viral proteins. That's why scientists have been working to use viruses as forces for good: to deliver useful ...

A UCLA study has found that a common strain of Caenorhabditis elegansa type of roundworm frequently used in laboratory research on neural developmenthas a pair of genes that encode both a poison and its antidote. The ...

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Stem cells in plants and animals behave surprisingly similarly - Phys.Org

Technology Networks

UK's Largest Resource of Human Stem Cells from Healthy Donors Unveiled Technology Networks The Human Induced Pluripotent Stem Cell Initiative (HipSci) project used standardised methods to generate iPSCs on a large scale to study the differences between healthy people. Reference sets of stem cells were generated from skin biopsies donated by ... and more »

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UK's Largest Resource of Human Stem Cells from Healthy Donors Unveiled - Technology Networks

May 10, 2017 Eye stem cells. Credit: University of Southampton

Reported in Nature today, one of the largest sets of high quality human induced pluripotent stem cell lines from healthy individuals has been produced by a consortium involving the Wellcome Trust Sanger Institute. Comprehensively annotated and available for independent research, the hundreds of stem cell lines are a powerful resource for scientists studying human development and disease.

With collaborative partners from King's College London, the European Bioinformatics Institute, the University of Dundee and the University of Cambridge, the study also investigates in unprecedented detail the extensive variation between stem cells from different healthy people.

Technological advancements have made it possible to take an adult cell and use specific growth conditions to turn back the clock - returning it to an early embryonic state. This results in an induced pluripotent stem cell (iPSC), which can develop into any type of cell in the body. These iPSCs have huge scientific potential for studying the development and the impact of diseases including cancer, Alzheimer's, and heart disease.

However, the process of creating an iPSC is long and complicated and few laboratories have the facilities to characterise their cells in a way that makes them useful for other scientists to use.

The Human Induced Pluripotent Stem Cell Initiative (HipSci) project used standardised methods to generate iPSCs on a large scale to study the differences between healthy people. Reference sets of stem cells were generated from skin biopsies donated by 301 healthy volunteers, creating multiple stem cell lines from each person.

The researchers created 711 cell lines and generated detailed information about their genome, the proteins expressed in them, and the cell biology of each cell line. Lines and data generated by this initiative are available to academic researchers and industry.

Dr Daniel Gaffney, a lead author on the paper, from the Wellcome Trust Sanger Institute, said: "We have created a comprehensive, high quality reference set of human induced pluripotent stem cell lines from healthy volunteers. Each of these stem cell lines has been extensively characterised and made available to the wider research community along with the annotation data. This resource is a stepping stone for researchers to make better cell models of many diseases, because they can study disease risk in many cell types, including those that are normally inaccessible."

By creating more than one stem cell line from each healthy individual, the researchers were able to determine the similarity of stem cell lines from the same person.

Prof Fiona Watt, a lead author on the paper and co-principal investigator of HipSci, from King's College London, said: "Many other efforts to create stem cells focus on rare diseases. In our study, stem cells have been produced from hundreds of healthy volunteers to study common genetic variation. We were able to show similar characteristics of iPS cells from the same person, and revealed that up to 46 per cent of the differences we saw in iPS cells were due to differences between individuals. These data will allow researchers to put disease variations in context with healthy people."

The project, which has taken 4 years to complete, required a multidisciplinary approach with many different collaborators, who specialised in different aspects of creating the cell lines and characterising the data.

Dr Oliver Stegle, a lead author on the paper, from the European Bioinformatics Institute, said: "This study was only possible due to the large scale, systematic production and characterisation of the stem cell lines. To help us to understand the different properties of the cells, we collected extensive data on multiple molecular layers, from the genome of the lines to their cell biology. This type of phenotyping required a whole facility rather than just a single lab, and will provide a huge resource to other scientists. Already, the data being generated have helped to gain a clearer picture of what a typical human iPSC cell looks like."

Dr Michael Dunn, Head of Genetics and Molecular Sciences at Wellcome, said: "This is the fantastic result of many years of work to create a national resource of high quality, well-characterised human induced pluripotent stem cells. This has been a significant achievement made possible by the collaboration of researchers across the country with joint funding provided by Wellcome and the MRC. It will help to provide the knowledge base to underpin a huge amount of future research into the effects of our genes on health and disease. By ensuring this resource is openly available to all, we hope that it will pave the way for many more fascinating discoveries."

Explore further: Stem cell consortium tackles complex genetic diseases

More information: Helena Kilpinen et al, Common genetic variation drives molecular heterogeneity in human iPSCs, Nature (2017). DOI: 10.1038/nature22403

http://www.yourgenome.org/facts/what-is-a-stem-cell

Reported in Nature today, one of the largest sets of high quality human induced pluripotent stem cell lines from healthy individuals has been produced by a consortium involving the Wellcome Trust Sanger Institute. Comprehensively ...

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Scientists unveil the UK's largest resource of human stem cells from healthy donors - Medical Xpress

Jonathan Pitre was exhausted on Tuesday, but he found some strength while watching the Ottawa Senators close out the New York Rangers in Game 6 of their second-round playoff series. -

His white blood cell count rising slowly, Jonathan Pitre will have a medical test Thursday to answer a crucial question: Are the new cells in his bloodstream genetically different?

The answer will reveal whether his second stem cell transplant has taken root in his bone marrow.

I want to be excited but Im holding back until we know for sure, said Pitres mother, Tina Boileau, who has been at his side in Minnesota since the transplant one month ago. Once we know, it seems like well be able to put one foot in front of the other and move on.

The family is taking a cautious approach since Pitres first transplant ended in disappointment in October when doctors learned that his own stem cells had recolonized his bone marrow.

Thursdays test will determine the source of Pitres new cells by isolating his white blood cells and examining the DNA they contain. All of Pitres cells will have a pair of X and Y chromosomes, but doctors will be hoping to find cells with a pair of X chromosomes since those cells can only come from his mother.

Such a discovery would provide evidence that the stem cells donated by Boileau have taken root in her sons bone marrow, and have started to produce new blood cells.

Im really hoping for a positive outcome; I think were due for good news, said Boileau, who expects to learn the results on Monday.

Pitre, who turns 17 next month, has seen his white blood cell count climb recently from 0.0 to 0.4, which remains well below the normal range of 4.0 to 11.0. He continues to suffer fevers, pain and profound exhaustion.

On Tuesday night, he watched the Ottawa Senators close out the New York Rangers while his mother applied fresh dressings and gauze after his bath. It was the first time in his life, Boileau said, that her son did not have the strength to stand during the procedure.

We had the game on and I have to say it really helped us get through it, said Boileau. Jonathan got a bit of strength from the excitement, and it was just enough to help me finish his dressings.

Pitre told his mother Tuesday night that hes not sure if he can see this one through.

I said, Youre going to have to because theres no way Im going home without you,' Boileau said. He managed to crack a little smile and said, OK, mom.

The University of Minnesota Masonic Childrens Hospital is theonly facility in the world that offers a blood and marrow transplant as a treatment for those with severe epidermolysis bullosa (EB). If Pitres transplant is successful, his new stems cells will have the power to deliver to his injured skin cells that can secrete a missing protein essential to the development of collagen.

Collagen is the glue that gives skin its strength and structure, and those with Pitres disease, recessive dytstrophic EB, are missing it. The treatment holds the potential to dramatically improve Pitres skin and make his disease more manageable.

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An exhausted Jonathan Pitre will soon learn if his stem cell transplant has worked - Ottawa Citizen

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Get burned over the weekend? RenovaCare has got your back. The New York-based biotech company has expertise in stem cells and organ regeneration, and has brought these skills to bear on wound care. One of the companys most promising methods uses a literal skin gun to spray skin stem cells on a burn or chronic wound to promote rapid healing. The healing is so rapid that you can walk into the hospital with a burn on a Friday night and return on Monday largelyhealed.

The skin gun process uses a patients stem cells, which are collected from healthy skin. The stem cells are isolated from the skin sample and suspended in a water solution that makes them easy to spray. Thecomputer-controlled skin gun works like the air brushes that are used by painters, but with much more precision.

The treatment is stupidly simple just spray the stem cells on the burned skin and wait for them to regrow. It is also extremely fast, taking only 1.5 hours to isolate the cells and and spray the skin. Once the skin cells are applied, it takes only a few days for the treatment to be effective. When state trooper Matthew Uram was burned in an unfortunate bonfire accident, he chose this experimental treatment and was entirely healed from his second-degree burns in four days.

This skin gun approach offers a significant improvement over the current methods of in-lab skin growth and surgical grafting that takes weeks and sometimes even months to be effective. Those who undergo these conventional skin graft techniques often suffer from infections and other setbacks, rendering the treatment far from optimal. A technology like the skin gun that could promote complete healing in a matter of days would represent a clear advance.

RenovaCares skin gun is still in the developmental stage and has not been approved by the FDA for sale in the United States, so you wont be able to find it on the shelves of burn units quite yet. The company is making progress towards that goal, however, and has recently announceda successful round of testing that shows its gun is capable of dispersing the skin cell liquid in a very uniform and dense manner.

Recent experiments conducted at Stem Cell Systems GmbH (Berlin, Germany) show that the gun can spray more than 20,000 evenly distributed droplets in a test area as compared to a conventional needle and syringe which produced only 91. The gun is not only capable of even dispersal, but it also is gentle on the skin stem cells, which retain 97.3 percent viability after SkinGun spraying. RenovaCare is continuing its research and development as it moves towards FDA approval and eventual commercial rollout. The company recently a filed a 510(k) submission with the FDA, which is a notice of intent to market a device and often is the first step before clinical trials.

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New Burn Healing Method uses Skin-Gun Stem-Cell Therapy ...

A molecular switch has been identified that converts skin cells into cells found in blood vessels, raising hopes of aiding heart disease sufferers.

This technique boosts levels of an enzyme that keeps cells young and could also potentially help cells avoid ageing as they are grown in the lab. Although this technique has been used before, this is the first time it has been understood by scientists.

Some techniques to convert mature skin cells into pluripotent stem cells use a cocktail of chemicals to ensure they turn into designated cell types. Other methods modify cells, skippingthe stem cell state completely. Recently, researchers have been exploring rewinding skin cells so they lose some of their mature cell identity.

Dr Jalees Rehman, who led the study at the University of Illinois at Chicago, said: They dont revert all the way back to a pluripotent stem cell, but instead turn into intermediate progenitor cells. Even though they only differentiate into a few different cell types, progenitor cells can be grown in large quantities, making them suitable for regenerative therapies.

Rehmans research group discovered that progenitor cells could be converted into blood vessel endothelial cells or erythrocytes depending on the level of a gene transcription factor called SOX17. When SOX17 levels were increased, progenitor cells were five times as likely to become endothelial cells. When this process was reversed, fewer endothelial cells but more erythrocytes were produced.

Dr Rehman said: It makes a lot of sense that SOX17 is involved because it is abundant in developing embryos when blood vessels are forming. When human progenitor cells were embedded into a gel implanted into mice, the cells formed functional human blood vessels. Mice that were suffering from heart damage formed functional human blood vessels in their hearts even interlinking with existing murine vessels to improve heart function.

During the course of the research, the scientists observed increased levels of telomerase the anti-ageing enzyme responsible for telomeres on the ends of chromosome in progenitor cells. The increase in telomerase we see in the progenitor cells could be an added benefit of using this partial de-differentiation technique for the production of new blood vessels for patients with cardiac disease, especially for older patients, said Dr Rehman. The process of converting and expanding these cells in the lab could make them age even further and impair their long-term function. But if the cells have elevated levels of telomerase, the cells are at lower risk of premature ageing.

Increased levels of telomerase are also observed in cancer cells, enabling cell division to occur at avery high rate. However, the scientists didnt observe any tumour formation during their research and their next steps will involve further research over a longer time period in larger animals. The study was published in Circulation.

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Protein enables scientists to convert skin to blood vessels - Lab News

Scientists may have found a cure for gray hair and baldness by accident Island Packet A protein commonly associated with nerve development, KROX20, turns on in skin cells that turn into a hair shaft. These cells then produce a protein called stem cell factor, which researchers said was key to pigmentation in hair. ... Le said the team's ... and more »

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Scientists may have found a cure for gray hair and baldness by accident - Island Packet

As we get older, many of us struggle with the harsh reality of our hair turning grey or falling out. But despite how common these problems are, scientists have struggled to identify their underlying biological cause, which means that we've been stuck using quick fixes such as hair dye and toupees to mask the problem.

Now, scientists have finally identified the specific cells that cause hair to grow and develop pigment in mice - a big step towards developing a treatment for grey hair and baldness.

The researchers actually stumbled upon these 'hair progenitor cells' by accident while researching a rare genetic disorder that causes tumours to grow on nerves, called Neurofibromatosis Type 1.

"Although this project was started in an effort to understand how certain kinds of tumours form, we ended up learning why hair turns grey and discovering the identity of the cell that directly gives rise to hair," saidlead researcher Lu Le from the University of Texas Southwestern Medical Centre.

"With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems."

Researchers already knew that skin stem cells contained in the bulge at the bottom of hair follicles were involved in hair growth, but they weren't quite sure what it was made these skin cells turn into hair cells. So they couldn't begin to find a way to target them or stimulate their growth.

But while researching tumour formation on nerve cells, they discovered the protein that sets these cells apart.

Called KROX20, the protein is more commonly associated with nerve development. But in hair follicles in mice the team discovered it switches on in skin cells that will go on to become the hair shaft that makes hair grow.

This protein then causes these cells to produce a protein called stem cell factor (SCF), and when both of these molecules are expressed in a cell, they move up the hair bulb, interact with pigment-producing melanocyte cells, and grow into healthy, coloured hairs.

But if one or the other is missing, the process goes wrong.When the team deleted the KROX20-producing cells, they found that no hair grew and mice became bald.

When they deleted the SCF gene in these hair-progenitor cells, the animal's hair turned white.

To be clear, this research has only been conducted in mice so far. While we have a lot of biological similarities with mice, the study needs to be repeated in humans before we can get too excited.

But Le and his team are already working on a project that will look for KROX20 and SCF in people with greying and thinning hair, in an attempt to work out whether it's associated with male pattern baldness in humans.

The hope is that it might not only teach us about why our hair changes as we get older, but also ageing in general. And the fact that the research could potentially lead to treatments that will help us look younger for longer doesn't hurt either.

The research has been published inGenes & Development.

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Scientists think they've finally found the mechanism behind grey hair and baldness - ScienceAlert

Bone marrow makes our red blood cells

DENNIS KUNKEL MICROSCOPY/SPL

By Helen Thomson

Scientists have engineered a bone-like implant to have its own working marrow that is capable of producing healthy blood. The implant may help treat several blood and immune disorders without the side effects of current treatments.

Bone marrow is the spongy tissue present inside the centre of bones. One of its jobs is to produce red blood cells from stem cells. Bone marrow transplants are sometimes needed to treat immune diseases that attack these stem cells, or in certain types of anaemia, in which the body cant make enough blood cells or clotting factors.

Such transplants involve replacing damaged marrow with bone marrow stem cells from a healthy donor. But first, the recipient must have their own bone marrow stem cells wiped out to make room for the transplanted donor cells. This is done using radiation and drugs, which can have serious side effects, such as nausea and loss of fertility.

To get round this problem, Shyni Varghese at the University of California, San Diego, and her colleagues have engineered an implant that resembles real bone. It provides a home for donor cells to grow and proliferate, bypassing the need for any drug and radiation treatment.

The implant has two main sections: an outer bone-like structure and an inner marrow, both engineered from a hydrogel matrix. Within the outer structure, calcium phosphate minerals help stem cells from the host grow into cells that help build bone. The inner matrix creates a home for donor bone marrow stem cells.

When placed beneath the skin in mice, the implant grew into a bone-like structure and produced a working marrow. Blood cells made by the donor stem cells inside the implant were able to get into circulation where they mixed with the hosts own blood cells. Six months later, blood cells from both the donor and host were still circulating around the body.

Its an additional accessory for the host, says Varghese. They have their own bone tissue and now an additional one that can be used if needed. Its like having more batteries for the bone.

Since the implant contributes to the hosts blood supply, rather than replacing it altogether, it cannot be used to treat people who have blood cancers, who would still need to have their own bone marrow stem cells wiped out to cure the disease.

Edward Gordon-Smith, emeritus professor of haemotology at St Georges University of London, says that the study isa splendid achievement.He says the structure could also offer a new way of studying blood stem cells and how blood disorders arise.

Journal reference: PNAS, DOI: 10.1073/pnas.1702576114

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Synthetic bone implant can make blood cells in its marrow - New Scientist

The newtechnique involves isolating and spraying the patient's own skin stem cells on the burn wounds

BURNS victims are being treated with an amazing gun which sprays them with stem cells and makes skin rapidly grow.

Treatment for people with extensive burns is a painful process and can often take weeks or months as surgeons take large sheets of skin from elsewhere on the body and graft it onto the affected area with the prospect of permanent scars a possibility.

Renova Care

Renova Care

Doctors in the US have developed the SkinGun, anew technique which involves isolating and spraying the patients own skin stem cells on the burn wounds.

Response to the SkinGun has been positive with patients saying their new skin is virtually indistinguishable from the rest of their body, the Daily Mail has reported.

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

The procedure involves a small patch of healthy skin being removed.

Then stem cells are separated out and placed in a solution which is then sprayed onto the wound.

The whole thing takes around 90 minutes.

Case studies include a 43-year-old man who suffered serious burns to his upper left arm, shoulder, back and torso after he was scalded by hot water and left him with huge welts.

Within six days new skin had formed over the wound and he was discharged from hospital.

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Burn victims treated with amazing gun which sprays them with stem ... - The Sun

Skin cells found at root of balding, gray hair Science Daily The researchers found that a protein called KROX20, more commonly associated with nerve development, in this case turns on in skin cells that become the hair shaft. These hair precursor, or progenitor, cells then produce a protein called stem cell ...

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Skin cells found at root of balding, gray hair - Science Daily

Ive been a fan of stem cells ever since I discovered ReLuma and AQ Skin Solutions, both of which use human conditioned media from adult adipose fat. Back then, it was a leap of face based on research surrounding stem cells and wound healing. Ever since, I have relied on my own experience and reports from the Truth In Aging community stem cells seem to work. So, I was excited (and vindicated) to read new research on stem cells and aging.

Researchers from the Perelman School of Medicine at the University of Pennsylvania found adult stem cells collected from human fat have a potential use to treat aging. Their findings are published in the journal, Stem Cells. The posh name for fat is adipose (worth keeping in mind if you want to bewilder a loved one by asking them if your bottom looks adipose in these pants). Anyway, adipose-derived stem cells (ASCs), create more proteins than researchers initially thought even when harvested from the elderly.

Our study shows these cells are very robust, even when they are collected from older patients, said Ivona Percec, M.D., director of Basic Science Research in the Center for Human Appearance and the study's lead author. It also shows these cells can be potentially used safely in the future because they require minimal manipulation and maintenance. Now, notice Dr. Percec uses the word safely. This is also a useful development, because we have never really known whether administering stem cells as anti-agers was really a safe thing to do.

Interestingly, adipose stem cells behave differently to other stem cells such as fibroblasts from the skin in that they are more stable over time and the rate at which they multiply stays consistent even as we age. I found some research from 2013 that speculated that these cells may be the same in infants through to the elderly. Dr. Perecs research seems to have clinched that this is indeed the case.

When you harvest adipose derived stem cells, they can become virtually any type of cell and put to the service of anti-aging, as well as healing purposes. Recent research has shown that they are a powerful source of skin regeneration because of their capability to provide not just cells but also tons of cytokines, or growth factors. The result, as one research paper puts it, is great promise for applications in repair of skin, rejuvenation of aging skin and aging-related skin lesions.

Adipose stem cells were discovered 40 years after the identification of bone marrow stem cells, opening up a new era of active stem cell therapy. It looks as if we are on the threshold of much more discovery in this field. For instance, Dr. Percec and her team are taking the research a step further to look at how tight the DNA is wound around proteins inside the cells and the way this affects aging.

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New Study Finds Human Fat Has Potential to Treat Aging - Truth In Aging

Science Daily

Scientists turn human induced pluripotent stem cells into lung cells ... Science Daily Scientists have announced two major findings that further our understanding of how stem cells become organs: the ability to grow and purify the earliest lung ... and more »

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Scientists turn human induced pluripotent stem cells into lung cells ... - Science Daily

STANFORD Stanford scientists have grown and assembled parts of a humanbrainin a dish.

Heres what is even more remarkable: Their mini-brain forms mental circuitry and cells converse with each other.

There is cross-talk, said lead researcher Dr. Sergiu Pasca, assistant professor of psychiatry and behavioral sciences at Stanford University School of Medicine, whose study was published in the journal Nature.

The team did not build an entire brain, the stuff of sci-fi fantasy. It doesnt think; its not self-aware. Thats a far more complex and likely unattainable goal.

Instead, they made a tiny but powerful model of the cerebral cortex for the study of such devastating human disorders as schizophrenia, epilepsy and autism impairments not easily studied in people.

This mini-brain reveals how networks of our mind can grow, behave and communicate, giving scientists an unprecedented view of our most mysterious organ.

What goes wrong with the mental circuitry of people with disease or disorders? Thats what they hope to learn.

Their brain also can be used to test potential drugs, essential for improving the pharmaceuticals need by psychiatry.

Its the first example of assembling, in a 3D culture, this brain region, Pasca said. Essentially, we get a small cerebral cortex in a dish.

The neurobiology of the brain remains one of the great challenges of modern medicine. Thats because we havent had direct views of the brains cellular behavior. While we can watch mental function through tools like Magnetic Resonance Imaging, that doesnt show us whats happening at the most basic level.

And we havent been able to watch brain development in the lab, because it happens during the second and third trimester of pregnancy.

Other diseases, like cancer, dont have this problem. Thats because doctors can sample tumor cells and look at them under a microscope. The sampling and study of brain cells is much harder.

Recapitulation of a pivotal stage in the cortexs formation demonstrates the techniques promise for discovery and even for testing potential interventions, according to a statement by Dr. Joshua Gordon, director of the National Institute of Mental Health, which made a videoto explain theresearch. It moves us closer to realizing the goal of precision medicine for brain disorders.

Members of the Stanford team started with longstanding tried-and-true techniques. They took skin cells and turned them into stem cells. Then they used chemical prods to turn them into two different types of brain cells.

In one dish, they grew cells called glutamatergic neurons, because they secrete the chemical glutamate, responsible for sending excitatory messages in the brain. Too much cellular excitement is thought to underlie conditions ilke seizures in epilepsy.

In a second dish, they grew cells that secrete a different chemical, called GABA, which sends inhibitory messages in the brain. Their job is to apply the brakes.

These arent just flat garden-variety layers of cells. Rather, theyre brainballs. Each ball measures about 1/16 of an inch in diameter and consists of over 1 million cells each, living for up to two years. They dont adhere to the dish; rather, they float, like little bobbing pearls.

Then they were introduced to each other.

And heres the magic: Within three days, the two cell types fused into one big sphere and then started organizing.

The cells that make GABA cells migrated over to the cells that make glutamate and began forming the circuitry that is responsible for the brains most advanced cognitive activities, the team found.

They start moving, and keep moving, for months, making small hops in one direction, said Pasca. They move to the other side and make connections.

They grew long appendages called axons. They also grew little knobby spines that stick out like branches to receive chemical messages from other cells axons. It is this signaling that enables us to think and learn.

Using small electrodes, the team listened in on the fused cells, and heard communication. The GABA-making and glutamatergic cells were successfully forming circuits and signaling to each other.

To be sure, their brainball is an incomplete model. It lacks complexity and is missing other cells that are part of the cerebral cortex. There arent blood vessels. It will never grow large.

But it is a powerful platform for asking how the human brain develops, said Pasca. Can we find abnormalities that are associated with disease? If we do, can we test drugs? That is its potential.

Already, its taught them about a rare developmental disease called Timothy syndrome, which includes symptoms of autism and epilepsy. Growing brainballs from skin cells donated by three patients, they found that these cells dont migrate normally their hopping movements are too quick, and too small. Over time, they got left behind.

The same gene that causes Timothy syndrome is linked to schizophrenia, other types of autism and bipolar disease. Pasca suspects these conditions may also have flaws in the fusing and communication of cells.

In the future, the Stanford team hopes to study the cells of individual patients to see if they can detect problems with their ability to move, migrate and communicate.

Stanfords Office of Technology Licensing has filed for a patent on the intellectual property involving the generation of these spheres and their assembly for studying development and disease.

The exquisite timing and placement of these different neuron cell types is critical for establishing a balance between excitation and inhibition within brain circuits. This balance is thought to be disrupted in brain disorders, Dr. David Panchision, chief of the NIMH Developmental Neurobiology Program (which funded the research), said in a statement. Re-playing these developmental processes with a patients own cells can allow us to determine what distinguishes these different disorders at a molecular and cellular level.

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Human brain in a dish: Stanford-grown brain cells fuse and chat - The Mercury News

Researchers have modified mouse stem cells to combat the kind of inflammation that arthritis and other conditions cause. The stem cells may one day be used in a vaccine that would fight arthritis and other chronic inflammation conditions in humans, a new paper suggests.

Such stem cells, known as SMART cells (Stem cells Modified for Autonomous Regenerative Therapy), develop into cartilage cells that produce a biologic anti-inflammatory drug that, ideally, will replace arthritic cartilage and simultaneously protect joints and other tissues from damage that occurs with chronic inflammation.

Researchers initially worked with skin cells from the tails of mice and converted those cells into stem cells. Then, using the gene-editing tool CRISPR in cells grown in culture, they removed a key gene in the inflammatory process and replaced it with a gene that releases a biologic drug that combats inflammation. The research is availablein the journal Stem Cell Reports.

Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed, says Farshid Guilak, the papers senior author and a professor of orthopedic surgery at Washington University School of Medicine. To do this, we needed to create a smart cell.

Many current drugs used to treat arthritisincluding Enbrel, Humira, and Remicadeattack an inflammation-promoting molecule called tumor necrosis factor-alpha (TNF-alpha). But the problem with these drugs is that they are given systemically rather than targeted to joints. As a result, they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections.

We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body, says Guilak, also a professor of developmental biology and of biomedical engineering and codirector of Washington Universitys Center of Regenerative Medicine.

If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint.

As part of the study, Guilak and his colleagues grew mouse stem cells in a test tube and then used CRISPR technology to replace a critical mediator of inflammation with a TNF-alpha inhibitor.

We hijacked an inflammatory pathway to create cells that produced a protective drug.

Exploiting tools from synthetic biology, we found we could re-code the program that stem cells use to orchestrate their response to inflammation, says Jonathan Brunger, the papers first author and a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco.

Over the course of a few days, the team directed the modified stem cells to grow into cartilage cells and produce cartilage tissue. Further experiments by the team showed that the engineered cartilage was protected from inflammation.

We hijacked an inflammatory pathway to create cells that produced a protective drug, Brunger says.

The researchers also encoded the stem/cartilage cells with genes that made the cells light up when responding to inflammation, so the scientists easily could determine when the cells were responding. Recently, Guilaks team has begun testing the engineered stem cells in mouse models of rheumatoid arthritis and other inflammatory diseases.

If the work can be replicated in animals and then developed into a clinical therapy, the engineered cells or cartilage grown from stem cells would respond to inflammation by releasing a biologic drugthe TNF-alpha inhibitorthat would protect the synthetic cartilage cells that Guilaks team created and the natural cartilage cells in specific joints.

When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation, Guilak explains. We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, its possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders.

With an eye toward further applications of this approach, Brunger adds, The ability to build living tissues from smart stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging of the National Institutes of Health supported this work. The Nancy Taylor Foundation for Chronic Diseases; the Arthritis Foundation; the National Science Foundation; and the Collaborative Research Center of the AO Foundation in Davos, Switzerland, provided additional funding.

Authors Farshid Guilak and Vincent Willard have a financial interest in Cytex Therapeutics of Durham, North Carolina, which may choose to license this technology. Cytex is a startup founded by some of the investigators. They could realize financial gain if the technology eventually is approved for clinical use.

Source: Washington University at St. Louis

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How 'smart' stem cells could lead to arthritis vaccine - Futurity - Futurity: Research News

An artist's impression of a reprogrammed stem cell.

Ella Marushchenko

In a curious confluence of the information technology industrys favourite word and scientists weakness for punning acronyms, researchers in St Louis, Missouri, in the US, have created what have been dubbed SMART cells.

SMART, in this case, stands for Stem cells Modified for Autonomous Regenerative Therapy, and their creation by a team based jointly at the Washington University School of Medicine and Shriners Hospital for Children promises a novel treatment for arthritis and other chronic conditions.

The team, led by Washington Universitys Farshid Guilak, reasoned that much of the pain and discomfort endured by arthritis suffers arises from inflammation caused by damaged cartilage. Reducing that inflammation, therefore, is an important therapeutic outcome.

To test this the team used mice. First, they harvested skin cells from tails, then turned them into stem cells. Next, using CRISPR gene-editing technology they excised a gene associated with inducing inflammation and replaced it with one that dampens it.

The resulting cells were then induced to grow into cartilage cells in cultures. The tissue thus produced was found to be free of inflammation.

In a clever move perhaps making the stem cells doubly smart Guilak and his colleagues further modified the stem cells so that they would light up when experiencing inflammation, making them easy to spot.

The research is published in in the journal Stem Cell Reports, and includes the news that research has now commenced using live mice.

Should the SMART cells eventually be found to be a viable avenue for human treatment, the results promise to be both more effective and better focused than existing arthritis drugs.

Pharmacological approaches to arthritis treatment mainly target the inflammation-promoting molecule called tumor necrosis factor alpha. The problem, however, is that they all do so on a system-wide basis, weakening the immune system and making patients more liable to infection.

We want to use our gene-editing technology as a way to deliver targeted therapy in response to localised inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body, says Guilak.

Study co-author Jonathan Brunger says the most pleasing aspect of the teams CRISPR-based approach is that it effectively highjacks the inflammatory pathway and turns it into a protective mechanism.

The ability to build living tissues from smart stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine, he adds.

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SMART cells to fight arthritis - Cosmos

Science Daily

Stem cells edited to fight arthritis: Goal is vaccine that targets ... Science Daily Using CRISPR technology, a team of researchers rewired stem cells' genetic circuits to produce an anti-inflammatory arthritis drug when the cells encounter ... Fighting arthritis: Researchers edit stem cells to fight inflammationKasmir Monitor CRISPR-SMART Cells Regenerate Cartilage, Secrete Anti-Arthritis DrugGenetic Engineering & Biotechnology News all 6 news articles »

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Stem cells edited to fight arthritis: Goal is vaccine that targets ... - Science Daily

Researchers at University of California, Irvine (UCI) have developed a method that can transform human skin cells into brain cells. With this amazing feat, scientists may be able to better understand what role inflammation plays in the progression of Alzheimers disease. And this knowledge could lay the groundwork towards developing more effective treatments and therapies to manage the condition.

Before this breakthrough, scientists relied mostly on mice microglia to study the immunology of Alzheimers. Microglia sometimes referred to as Hortega cells are a special kind of cell that can be found in the human brain and spinal cord. The primary role of these cells is to protect the brain and the spine from infections, disease and any invading microbe. They provide immune support for the entire central nervous system by removing dead cells, damaged cells and other debris.

Along this line, microglial cells also help keep healthy cells from degenerating managing inflammation as well as developing and maintaining the integrity of neural networks which is why they are believed to play a special role in delaying the progression of neurodegenerative conditions like Alzheimers.

While studying brain cells from mice is useful, studying the real thing is, of course, more preferable. And the method developed by the UCI team is a step in this direction.

Using skin cells donated by UCI Alzheimers Disease Research Center patients, the UCI team led by Edsel Abud, Mathew Blurton-Jones and Wayne Poon made use of a genetic process to reprogram the skin cells and turn them into induced pluripotent cells (iPSCs) adult cells that are modified to act like embryonic stem cells which can turn into any kind of cell or tissue. The iPSCs were then exposed to a series of differentiation factors which mimicked the developmental origin of microglia. This exposure resulted in cells that are pretty much like human microglial cells.

Instead of continuing to rely on mice microglial cells, scientists now have a more realistic model for studying human disease in order to develop new and better therapies. And they have now started on this new path. They are using the microglial-like cells in 3D brain models so they can study how these cells interact with other brain cells and understand how this interaction impacts the progression of Alzheimers and the development of other neurological conditions.

As explained by Professor Blurton-Jones in a statement they issued: Microglia play an important role in Alzheimers and other diseases of the central nervous system. Recent research has revealed that newly discovered Alzheimers-risk genes influence microglia behavior. Using these cells, we can understand the biology of these genes and test potential new therapies.

This latest breakthrough is once again proving how important stem cells are in helping understand biological processes, both under normal conditions and under disease-related conditions. Eventually, scientists are bound to stumble on that ultimate discovery that can hopefully be instrumental in combating diseases right at their source, so we can stop dealing with devastating diseases, especially those that affect the brain and threaten a persons life.

The study was recently published in the journal Neuron.

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Scientists Can Now Turn Human Skin Cells Into Brain Cells - Wall Street Pit

In a major development, researchers have developed a cartilage that fights inflammation caused by arthritis and other chronic conditions, using the gene-editing technique called CRISPR. For the breakthrough, researchers at Washington University School of Medicine converted skin cells from the tails of mice into stem cells. They then used the gene-editing tool CRISPR to remove a gene involved in inflammation and replace it with one that produces anti-inflammatory drug. They called the resulting cells as SMART cells, which stands for Stem cells Modified for Autonomous Regenerative Therapy. "Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed," said Farshid Guilak, Professor at Washington University School of Medicine, and senior author of a study published online in the journal Stem Cell Reports. "To do this, we needed to create a 'smart' cell," Guilak said. According to the study, SMART cells, develop into cartilage cells that produce a biologic anti-inflammatory drug that could replace arthritic cartilage and simultaneously protect joints and other tissues from damage that occurs with chronic inflammation. Many current drugs used to treat arthritis attack an inflammation-promoting molecule called tumour necrosis factor-alpha (TNF-alpha). But the problem with these drugs is that they are given systemically rather than targeted to joints. As a result, they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections. "We want to use our gene-editing technology as a way to deliver targeted therapy in response to localised inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body," Guilak said. The research has been published in the journal Stem Cell Reports.

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Fighting arthritis: Researchers edit stem cells to fight inflammation - Kasmir Monitor

NEW YORK & PITTSBURGH--(BUSINESS WIRE)--RenovaCare, Inc., (OTCQB: RCAR), highlighted an analysis of treatment results on a variety of wide-area and severe burn injuries published in Burns, the peer-reviewed Journal of the International Society for Burn Injuries. The treatment method, which involved isolating and spraying the patients own skin stem cells on the burn wounds, is the technology underlying RenovaCares patented CellMist and SkinGun*.

The early cell spray technology which was used to successfully treat a wide spectrum of burn injuries to some of the largest body areas ever treated with stem cell transplantation, has been engineered into todays RenovaCare SkinGun device, explained Mr. Thomas Bold, President and CEO of RenovaCare, Inc.

The results, published in August 2016, report the retrospective analysis of outcomes in 45 severe second-degree burn patients who received skin stem cell spray grafting treatment under an innovative practice approach.

The patients suffered burn wounds such as gas and chemical explosions, as well as electrical, gasoline, hot water and tar scalding burns. Click here to see before-after photos

In the case of one patient with severe electrical burns to over one-third of his body, his wounds were sprayed with 23 million stem cells isolated from a tiny 2 x 2 sample of his own skin. Within five days of treatment, his chest and arms were already healed. Four days later, the patient was discharged from the hospital, said Mr. Bold.

These published analyses are especially encouraging to us because patients were successfully treated with the technology no matter what the source of the burn, concluded Mr. Bold.

Six Burn Causes: Patient Results and Photos Click here to see before-after photos

According to the Burns article authors, regardless of the burn type, cell spray showed quick healing (fast epithelialization), along with other benefits. "Cell-spray grafting is also especially suitable for hands and joint areas, where prolonged times to re-epithelization may significantly impact functionality and esthetic outcome," said the report.

Other findings in the article, following cell spray with the technology include:

Gas Explosion Patient

A gas explosion caused burns to the upper right arm and partial right chest area of a 43-year-old man who also suffered orthopedic injuries. "There was no evidence of hypertrophic (abnormalenlargementofanorgan) scarring throughout the prior burn area, and his only functional impairment ... was due to his wrist injury," concluded the report.

Chemical Explosion Burn

A 37-year-old patient suffered serious burns to his arms and hands as a result of a potassium nitrate explosion. The report observed the following outcome: "... the areas of autografts were noted to be almost indiscernible with the normal skin ... The patient maintained a full range of motion in all extremities without restriction."

Electrical Burn

After grabbing a live electrical wire a 35-year-old male received deep burns to the head, chest, abdomen, back, right hand and foot. Doctors indicated a full recovery to the affected areas in the article: ... all of the areas treated with cell spray grafting were noted as completely healed and re-epithelialized ... the patient had a functional range of motion in all extremities."

Gasoline Flame Burn

A gasoline flame injury to an 18-year-old male resulted in burns to the arms and legs. Forty-five million cells were obtained from the patient and used to spray the entire burn wound surface. "Wounds were completely healed by ... and there was no evidence of ... scarring or contractures, and the patient demonstrated a full range of motion in all extremities," the article said.

Hot Water Scalding

A hot water scalding injury covered a 43-year-old patients upper left arm, shoulder, back and torso. His post cell spray treatment provided the following results: "A 100% re-epithelialization was noted and the patient was discharged that day with instructions to apply Eucerin moisturizer to the wound ... the patient was also noted to have a full range of motion in his extremities, according to the article.

Hot Tar Scalding

Hot tar burned a 43-year-old mans right arm, right hand and midsection and within seven days of treatment the article concluded: all areas were noted to be healed and re-epithelialized and the patient was discharged.

The Burns article titled, Second-degree burns with six etiologies treated with autologous noncultured cell-spray grafting, by: Roger Esteban-Vives, Myung S. Choi, Matthew T. Young, Patrick Over, Jenny Ziembicki, Alain Corcos, and Jrg Gerlach, was published by Elsevier in the November 2016 issue of Burns (Nov;42(7):e99-e106. doi: 10.1016/j.burns.2016.02.020. Epub 2016 Aug 25).

Copies of the article are available to credentialed journalists upon request; please contact Elsevier's Newsroom at newsroom@elsevier.com or+31 20 485 2492.

Study authors, Dr. Roger Esteban-Vives and Dr. Jrg Gerlach currently have a financial interest in the SkinGun spray-grafting technology through payments from RenovaCare, Inc. Dr. Esteban-Vives, who currently Director of Cell Sciences at RenovaCare, Inc., was a postdoctoral fellow at the University of Pittsburgh when this work was conducted and did not have such financial interest at that time.

*RenovaCare products are currently in development.They are not available for sale in theUnited States. There is no assurance that the companys planned or filed submissions to the U.S. Food and Drug Administration, if any, will be accepted or cleared by the FDA.

AboutBurns

Burnsaims to foster the exchange of information among all engaged in preventing and treating the effects of burns. The journal focuses on clinical, scientific and social aspects of these injuries and covers the prevention of the injury, the epidemiology of such injuries and all aspects of treatment including development of new techniques and technologies and verification of existing ones. Regular features include clinical and scientific papers, state of the art reviews and descriptions of burn-care in practice.

About RenovaCare

RenovaCare, Inc. is developing first-of-its-kind autologous (self-donated) stem cell therapies for the regeneration of human organs. Its initial product under development targets the bodys largest organ, the skin. The companys flagship technology, the CellMist System, uses its patented SkinGun to spray a liquid suspension of a patients stem cells the CellMist Solution onto wounds. RenovaCare is developing its CellMist System as a promising new alternative for patients suffering from burns, chronic and acute wounds, and scars. In the US alone, this $45 billion market is greater than the spending on high-blood pressure management, cholesterol treatments, and back pain therapeutics.

For additional information, please call Drew Danielson at: 888-398-0202 or visit: http://renovacareinc.com

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Investors and others should note that we announce material financial information to our investors using SEC filings and press releases. We use our website and social media to communicate with our subscribers, shareholders and the public about the company, RenovaCare, Inc. development, and other corporate matters that are in the public domain. At this time, the company will not post information on social media that could be deemed to be material information unless that information was distributed to public distribution channels first. We encourage investors, the media, and others interested in the company to review the information we post on the companys website and the social media channels listed below:

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Legal Notice Regarding Forward-Looking Statements

No statement herein should be considered an offer or a solicitation of an offer for the purchase or sale of any securities. This release contains forward-looking statements that are based upon current expectations or beliefs, as well as a number of assumptions about future events. Although RenovaCare, Inc. (the Company) believes that the expectations reflected in the forward-looking statements and the assumptions upon which they are based are reasonable, it can give no assurance that such expectations and assumptions will prove to have been correct. Forward-looking statements, which involve assumptions and describe our future plans, strategies, and expectations, are generally identifiable by use of the words may, will, should, could, expect, anticipate, estimate, believe, intend, or project or the negative of these words or other variations on these words or comparable terminology. The reader is cautioned not to put undue reliance on these forward-looking statements, as these statements are subject to numerous factors and uncertainties, including but not limited to: the timing and success of clinical and preclinical studies of product candidates, the potential timing and success of the Companys product programs through their individual product development and regulatory approval processes, adverse economic conditions, intense competition, lack of meaningful research results, entry of new competitors and products, inadequate capital, unexpected costs and operating deficits, increases in general and administrative costs, termination of contracts or agreements, obsolescence of the Company's technologies, technical problems with the Company's research, price increases for supplies and components, litigation and administrative proceedings involving the Company, the possible acquisition of new businesses or technologies that result in operating losses or that do not perform as anticipated, unanticipated losses, the possible fluctuation and volatility of the Company's operating results, financial condition and stock price, losses incurred in litigating and settling cases, dilution in the Company's ownership of its business, adverse publicity and news coverage, inability to carry out research, development and commercialization plans, loss or retirement of key executives and research scientists, and other risks. There can be no assurance that further research and development will validate and support the results of our preliminary research and studies. Further, there can be no assurance that the necessary regulatory approvals will be obtained or that the Company will be able to develop commercially viable products on the basis of its technologies. In addition, other factors that could cause actual results to differ materially are discussed in the Company's most recent Form 10-Q and Form 10-K filings with the Securities and Exchange Commission. These reports and filings may be inspected and copied at the Public Reference Room maintained by the U.S. Securities & Exchange Commission at 100 F Street, N.E., Washington, D.C. 20549. You can obtain information about operation of the Public Reference Room by calling the U.S. Securities & Exchange Commission at 1-800-SEC-0330. The U.S. Securities & Exchange Commission also maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the U.S. Securities & Exchange Commission athttp://www.sec.gov. The Company undertakes no obligation to publicly release the results of any revisions to these forward-looking statements that may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.

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Outcomes of Burn Patients Treated with Cell Spray Technology ... - Business Wire (press release)

An artist's impression of the reengineered cell that produces an anti-inflammatory drug when it encounters inflammation (Credit: Ella Marushchenko)

Combining two cellular-editing processes, researchers have developed cartilage that fights inflammation. The scientists hope that the breakthrough could eventually lead to localized injections that combat arthritis or perhaps a vaccine that would eliminate the condition altogether.

Like many of the biology breakthroughs happening today, the WU researchers started with stem cells. To be more accurate, they actually started with skin cells from the tails of mice and converted them into stem cells. They then used a gene-editing technique called CRISPR to remove a gene involved in inflammation and replace it with one that releases an anti-inflammatory drug. The resulting cells are known as SMART cells, which stands for Stem cells Modified for Autonomous Regenerative Therapy.

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"Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed," said Farshid Guilak, the senior author of a paper about the work and a professor of orthopedic surgery at Washington University School of Medicine. "To do this, we needed to create a 'smart' cell."

As part of the current fight against arthritis, there are several drugs that work to eliminate an inflammatory molecule called tumor necrosis factor-alpha (TNF-alpha). The issue with such drugs, however, is that they work throughout the entire body, rather than only at the site of inflammation, and can have an impact on the body's overall immune system.

To change this dynamic, the researchers replaced the gene that expresses TNF-alpha with one that inhibits it by releasing a drug, basically converting the cells from those that create inflammation to those that fight it. "We hijacked an inflammatory pathway to create cells that produced a protective drug," said Jonathan Brunger, a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco. They then coaxed these cells to grow into cartilage in the lab which, they found, was successful in combating inflammation.

The hope is that injecting the cells into areas afflicted by arthritis, the new anti-inflammatory cartilage could replace the old cartilage. This would effectively create a vaccine against the condition, as the newly engineered cells would only release the anti-inflammatory drug when inflammation is present such as during an arthritic flare-up and turn off the release of the drug when the flare subsides.

Additionally, the researchers also engineered the new cells to light up when they responded to inflammation so that they could track their response in the body. The cells are now being tested in mice with rheumatoid arthritis and other inflammatory disorders and the researchers think that the method of combining stem cells with CRISPR could help fight other diseases as well.

"We believe this strategy also may work for other systems that depend on a feedback loop," said Guilak. "In diabetes, for example, it's possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders."

The paper is published in the journal Stem Cell Reports.

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SMART cells open door to arthritis vaccine - New Atlas

Cancerous cells in a skin tumor become locked in an abnormal state as a result of the activation of a gene-regulating element (green).

Like an image in a broken mirror, a tumor is a distorted likeness of a wound. Scientists have long seen parallels between the two, such as the formation of new blood vessels, which occurs as part of both wound healing and malignancy.

Research at The Rockefeller University offers new insights about what the two processes have in commonand how they differat the molecular level. The findings, described April 20 in Cell, may aid in the development of new therapies for cancer.

Losing identity

At the core of both malignancy and tissue mending are stem cells, which multiply to produce new tissue to fill the breach or enlarge the tumor. To see how stem cells behave in these scenarios, a team led by scientists in Elaine Fuchss lab compared two distinct types found within mouse skin.

One set of stem cells, at the base of the follicle, differentiates to form the hair shaft; while another set produces new skin cells. Under normal conditions, these two cell populations are physically distinct, producing only their respective tissue, nothing else.

But when Yejing Ge, a postdoc in the Fuchs lab, looked closely at gene activity in skin tumors, she found a remarkable convergence: The follicle stem cells expressed genes normally reserved for skin stem cells, and vice versa. Around wounds, the researchers documented the same blurring between the sets of stem cells.

Master switches

Two of the identity-related genes stood out. They code for so-called master regulators, molecules that play a dominant role in determining what type of tissue a stem cell will ultimately producein this case, hair follicle or skin. The researchers suspect that stress signals from the tissue surrounding the damage or malignancy kick off a cycle that feeds off itself by enabling the master regulators to make more of themselves.

Access to DNA is the key. To go to work, master regulators bind to certain regions of DNA and so initiate dramatic changes in gene expression. The researchers found evidence that stress signals open up new regions of DNA, making them more accessible to gene activation. By binding in these newly available spots, master regulators elevate the expression of identity-related genes, including the genes that encode the master regulators themselves.

Locked in

While wounds heal, cancer can grow indefinitely. The researchers discovered that while stress signals eventually wane in healing wounds, they can persist in cancerand with prolonged stress signaling, another region of DNA opens up to kick off a separate round of cancer-specific changes.

Tumors have been described as wounds that never heal, and now we have identified specific regulatory elements that, when activated, keep tumor cells locked into a blurred identity, Ge says.

The scientists hope this discovery could lead to precise treatments for cancer that cause less collateral damage than conventional chemotherapy. We are currently testing the specificity of these cancer regulatory elements in human cells for their possible use in therapies aimed at killing the tumor cells and leaving the healthy tissue cells unharmed, Fuchs says.

Elaine Fuchs is the Rebecca C. Lancefield Professor, head of the Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, and a Howard Hughes Medical Institute investigator.

Excerpt from:
A mechanism shared by healing wounds and growing tumors - The Rockefeller University Newswire

A New Type of Stem Cell

While much has been gleaned about the power of stem cells over the last few decades, researchers from the Salk Institute and Peking Universityin China recently found out theres plenty left to discover and invent. Nature, it seems, will always keep you guessing.

In a study published in the journal Cell, the team of researchers revealed they had succeeded in creating a new kind of stem cell thats capable of becoming any type of cell in the human body. Extended pluripotent stem cells or EPS cells are similar to induced pluripotent stem cells(iPS cells), which were invented in 2006.

The key difference between the two is that iPS cells are made from skin cells (called fibroblasts) and EPS cells are made from a combination of skin cells and embryonic stem cells. iPS cells are the hallmark of stem cell research and can be programmed to become any cell in the human body hence the pluripotent part of their name. EPS cells, too, can give rise to any type of cell in the human body, but they can also do something very different something unprecedented, actually: they can create the tissues needed to nourish and grow an embryo.

The discovery of EPS cells provides a potential opportunity for developing a universal method to establish stem cells that have extended developmental potency in mammals, says Jun Wu, one of the studys authors and senior scientist at the Salk Institute, in the organizations news release.

When a human or any mammalian egg gets fertilized, the cells divide up into two task forces: one set is responsible for creating the embryo, and the other set creates the placenta and other supportive tissues needed for the embryo to survive (called extra-embryonic tissues). This happens very early in the reproductive process so early, in fact, that researchers have had a very hard time recreating it in a lab setting.

By culturing and studying both types of cells in action, researchers would not only be able to understand the mechanism that drives it, but hopefully could shed some light on what happens when things go wrong, like in the case of miscarriage.

The researchers at the Salk Institute managed to form a chemical cocktail of four chemicals and a type of growth factor that created a stable environment in which they could culture both types of cells in an immature state. They could then harness the two types of cells for their respective abilities.

What they discovered was that not only were these cells extremely useful for creating chimeras (where two types of animal cells or human and animal cells are mixed to form something new), but were also technically capable of creating and sustaining an entire embryo.At least in theory: while they were able to sustain both human and mouse cells, the ethical considerations of creating a human embryo this way have prevented them from attempting it.

That being said, theres no shortage of applications for this type of stem cell: researchers will be able to use them to model diseases, regenerate tissue, create and trial drug therapies, and study in depth early reproductive processes like implantation. Human-animal chimeras may also help engineer organs for transplant or, you know, give rise to the next superhero.

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Researchers Invent Stem Cell Capable of Becoming an Entire Embryo - Futurism

Using human skin cells, University of California, Irvine neurobiologists and their colleagues have created a method to generate one of the principle cell types of the brain called microglia, which play a key role in preserving the function of neural networks and responding to injury and disease.

The finding marks an important step in the use of induced pluripotent stem (iPS) cells for targeted approaches to better understand and potentially treat neurological diseases such as Alzheimer's. These iPS cells are derived from existing adult skin cells and show increasing utility as a promising approach for studying human disease and developing new therapies.

Skin cells were donated from patients at the UCI Alzheimer's Disease Research Center. The study, led by Edsel Abud, Wayne Poon and Mathew Blurton Jones of UCI, used a genetic process to reprogram these cells into a pluripotent state capable of developing into any type of cell or tissue of the body.

The researchers then guided these pluripotent cells to a new state by exposing the cells to a series of differentiation factors which mimicked the developmental origin of microglia. The resulting cells act very much like human microglial cells. Their study appears in the current issue of Neuron.

In the brain, microglia mediate inflammation and the removal of dead cells and debris. These cells make up 10- to 15-percent of brain cells and are needed for the development and maintenance of neural networks.

"Microglia play an important role in Alzheimer's and other diseases of the central nervous system. Recent research has revealed that newly discovered Alzheimer's-risk genes influence microglia behavior. Using these cells, we can understand the biology of these genes and test potential new therapies," said Blurton-Jones, an assistant professor of the Department of Neurobiology & Behavior and Director of the ADRC iPS Core.

"Scientists have had to rely on mouse microglia to study the immunology of AD. This discovery provides a powerful new approach to better model human disease and develop new therapies," added Poon, a UCI MIND associate researcher.

Along those lines, the researchers examined the genetic and physical interactions between Alzheimer's disease pathology and iPS-microglia. They are now using these cells in three-dimensional brain models to understand how microglia interact with other brain cells and influence AD and the development of other neurological diseases.

"Our findings provide a renewable and high-throughput method for understanding the role of inflammation in Alzheimer's disease using human cells," said Abud, an M.D./Ph.D. student. "These translational studies will better inform disease-modulating therapeutic strategies."

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Skin stem cells used to generate new brain cells: Study to advance ... - Science Daily

From Skin to Brain

The brain is one of the most vital organs in the human body, so damage to the brain from injury or aging can have major impacts on peoples quality of life.Neurological disorders representsome of todays most devastating medical conditions that are also difficult to treat.Among these is Alzheimers disease.

Usually, research involving Alzheimers rely on brain cells from mice. Now, neurobiologists from the University of California, Irvine (UCI) have developed a method that could allow the use of human cells instead of animal ones to help understand neurological diseases better.

In their study, which was published in the journal Neuron, the researchers found a way to transform human skin cells into stem cells and program them into microglial cells. The latter make up about 10 to 15 percent of the brain and are involved in the removing dead cells and debris, as well as managing inflammation. Micgrolia are instramentalin neural network development and maintenance, explained researcher Mathew Blurton Jones, fromUCIs Department of Neurobiology & Behavior.

Microglia play an important role in Alzheimers and other diseases of the central nervous system. Recent research has revealed that newly discovered Alzheimers-risk genes influence microglia behavior, Jones said in an interview for a UCI press release. Using these cells, we can understand the biology of these genes and test potential new therapies.

The skin cells had been donated by patients from UCIs Alzheimers Disease Research Center. These were firstsubjected toa genetic process to convert them into induced pluripotent stem (iPS) cells adult cells modified to behave as an embryonic stem cell, allowing them to become other kinds of cells. These iPS cells were then exposed to differentiation factors designed to imitate the environment of developing microglia, which transformed them into the brain cells.

This discovery provides a powerful new approach to better model human disease and develop new therapies, said UCI MIND associate researcher Wayne Poon in the press release. The researchers, in effect, have developed a renewable and high-throughput method for understanding the role of inflammation in Alzheimers disease using human cells, according to researcher Edsel Abud in the same source.

In other words, by using human microglia instead of those from mice, the researchers have developed a more accurate toolto study neurological diseases and to develop more targeted treatment approaches. In the case of Alzheimers, they studied the genetic and physical interactions between the diseases pathology and the induced microglia cells. These translational studies will better inform disease-modulating therapeutic strategies, Abud added in the press release.

Furthermore, they are now using these induced microglia cells in three-dimensional brain models. The goal is to understand the interaction between microglia and other brain cells, and how these influence the development of Alzheimers and other neurological diseases.

This is all made possible by reprogrammable stem cells. Indeed, this study is one more example of how stem cells arechanging medicine.

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A New Technique Transforms Human Skin Into Brain Cells - Futurism