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Scientists unveil the UK’s largest resource of human stem cells from healthy donors – Science Daily

By Dr. Matthew Watson

Scientists unveil the UK's largest resource of human stem cells from healthy donors
Science Daily
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 ...

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

By raymumme

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

By JoanneRUSSELL25

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

By JoanneRUSSELL25

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

By JoanneRUSSELL25

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

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Scientists think they’ve finally found the mechanism behind grey hair and baldness – ScienceAlert

By Sykes24Tracey

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

By Dr. Matthew Watson

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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Burn victims treated with amazing gun which sprays them with stem cells and makes skin grow – The Sun

By JoanneRUSSELL25

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

By daniellenierenberg

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

By LizaAVILA

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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Scientists turn human induced pluripotent stem cells into lung cells – Science Daily

By LizaAVILA


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Scientists turn human induced pluripotent stem cells into lung cells
Science Daily
CReM scientists work with induced pluripotent stem cells, or iPSCs, which were discovered by Shinya Yamanaka in 2006. Yamanaka figured out how to take an adult cell in the human body -- like a blood cell or skin cell -- and "reprogram" it into a stem ...

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How ‘smart’ stem cells could lead to arthritis vaccine – Futurity: Research News

By Sykes24Tracey

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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SMART cells to fight arthritis – Cosmos

By raymumme

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

By Sykes24Tracey

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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Stem cells edited to fight arthritis: Goal is vaccine that targets … – Science Daily

By raymumme


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

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Skin stem cells used to generate new brain cells

By Sykes24Tracey

April 25, 2017 Credit: University of California, Irvine

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."

Explore further: 'Housekeepers' of the brain renew themselves more quickly than first thought

More information: Edsel M. Abud et al, iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases, Neuron (2017). DOI: 10.1016/j.neuron.2017.03.042

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Stem Cells Edited to Fight Arthritis – Technology Networks

By daniellenierenberg


Technology Networks
Stem Cells Edited to Fight Arthritis
Technology Networks
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 ...
CRISPR-SMART Cells Regenerate Cartilage, Secrete Anti-Arthritis DrugGenetic Engineering & Biotechnology News

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‘Minibrains’ in a dish shed a little light on autism and epilepsy – 89.3 KPCC

By daniellenierenberg

Tiny, 3-D clusters of human brain cells grown in a petri dish are providing hints about the origins of disorders like autism and epilepsy.

An experiment using these cell clusters which are only about the size of the head of a pin found that a genetic mutation associated with both autism and epilepsy kept developing cells from migrating normally from one cluster of brain cells to another, researchers report in the journal Nature.

"They were sort of left behind," says Dr. Sergiu Pasca, an assistant professor of psychiatry and behavioral sciences at Stanford. And that type of delay could be enough to disrupt the precise timing required for an actual brain to develop normally, he says.

The clusters often called minibrains, organoids or spheroids are created by transforming skin cells from a person into neural stem cells. These stem cells can then grow into structures like those found in the brain and even form networks of communicating cells.

Brain organoids cannot grow beyond a few millimeters in size or perform the functions of a complete brain. But they give scientists a way to study how parts of the brain develop during pregnancy.

"One can really understand both a process of normal human brain development, which we frankly don't understand very well, [and] also what goes wrong in the brain of patients affected by diseases," says Paola Arlotta, a professor of stem cell and regenerative biology at Harvard who was not involved in the cell migration study. Arlotta is an author of a second paper in Nature about creating a wide variety of brain cells in brain organoids.

Pasca's team began experimenting with organoids in an effort to learn more about brain disorders that begin long before birth. Animal brains are of limited use in this regard because they don't develop the way human brains do. And traditional brain cell cultures, which grow as a two-dimensional layer in a dish, don't develop the sort of networks and connections that are thought to go awry in disorders like autism, epilepsy and schizophrenia.

"So the question was really, can we capture in a dish more of these elaborate processes that are underlying brain development and brain function," Pasca says.

He was especially interested in a critical process that occurs when cells from deep in the brain migrate to areas nearer the surface. This usually happens during the second and third trimesters of pregnancy.

So Pasca's team set out to replicate this migration in a petri dish. They grew two types of clusters, representing both deep and surface areas of the forebrain. Then they placed deep clusters next to surface clusters to see whether cells would start migrating.

Pasca says the cells did migrate, in a surprising way. "They don't just simply crawl, but they actually jump," he says. "So they look for a few hours in the direction in which they want to move, they sort of decide on what they want to do, and then suddenly they make a jump."

Pasca suspected this migration process might be disrupted by a genetic disorder called Timothy syndrome, which can cause a form of autism and epilepsy. So he repeated the experiment, using stem cells derived from the skin cells of a person who had Timothy syndrome.

And sure enough, the cells carrying the genetic mutation didn't jump as far as healthy cells did. "They moved inefficiently," Pasca says.

Next Pasca wondered if there might be some way to fix the migration problem. He thought there might be, because Timothy syndrome causes cells to let in too much calcium. And he knew that several existing blood pressure drugs work by blocking calcium from entering cells.

So the team tried adding one of these calcium blockers to the petri dish containing clusters of brain cells that weren't migrating normally. And it worked. "If you do treat the cultures with this calcium blocker, you can actually restore the migration of cells in a dish," Pasca says.

Fixing the problem in a developing baby wouldn't be that simple, he says. But the experiment offers a powerful example of how brain organoids offer a way to not only see what's going wrong, but try drugs that might fix the problem.

Still, to realize their full potential, brain organoids need to get better, Arlotta says. This means finding ways to keep the cell clusters alive longer and allowing them to form more of the types of brain cells that are found in a mature brain.

Arlotta's team has developed techniques that allow brain cell clusters to continue growing and developing in a dish for many months. And what's remarkable, she says, is that over time the clusters automatically begin creating structures and networks like those in a developing brain.

"Using their own information from their genome, the cells can self-assemble and they can decide to become a variety of different cell types than you normally find," she says.

In one experiment, a brain organoid produced nearly all the cell types found in the mature retina, Arlotta says. And tests showed that some of these retinal cells even responded to light.

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A mechanism shared by healing wounds and growing tumors – The Rockefeller University Newswire

By NEVAGiles23

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.

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

By raymumme

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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