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Newswise NIBIB-funded researchers report in a recent study that they were able to use human stem cells to grow brand new nerves in a rat model of spinal cord injury. The neurons grew tens of thousands of axons that extended the entire length of the spinal cord, out from the area of injury. The procedure employs induced pluripotent stem cells or iPSCs, which are stem cells that can be driven to become a specific cell type -- in this case nerve cells-- to repair an experimentally damaged spinal cord. The iPSCs were made using the skin cells of an 86 year old male, demonstrating that even in an individual of advanced age, the ability of the cells to be turned into a different cell type (pluripotency) remained.

Lead author Paul Lu, Ph.D., and senior author Mark Tuszynski, MD, PhD, and their team at the University of California - San Diego Center for Neural Repair, performed the experiment building on earlier work using human embryonic stem cells in a similar rat spinal cord injury model.1 The current work, described in the August 20 edition of Neuron, was performed to determine whether iPSCs could be used for spinal cord repair.2

The group is interested in using iPSCs to develop a potential repair for spinal cord injury (SCI) because with iPSCs, they can use cells taken from the person with the injury, rather than use donated cells such as human embryonic stem cells, which are foreign to the patient. This is an important advantage because it avoids any immune rejection that could occur with foreign repair cells.

In the current work, the iPSC-derived human neurons were embedded in a matrix that included a cocktail of growth factors, which was grafted onto the experimentally injured spinal cord in the rat model. After three months the researchers observed extensive axonal growth projecting from the grafted neurons, reaching long distances in both directions along the spinal cord, from the brain to the tail end of the spinal cord. The axons appeared to make connections with the existing rat neurons. Importantly, the axons extended out from the site of injury, an area with a complex combination of post-injury factors and processes going on, some of which are known to hinder neuronal growth and axon extension.

In the earlier study, Tuszynski and colleagues used human embryonic stem cells in a similar grafting experiment. In that study, axons grew out from the site of spinal cord injury and the treated animals had some restoration of ability to move affected limbs. The current study was undertaken to see if the same result could be achieved using the iPSC method to create the neurons used in the graft. While the use of iPSCs in the current study resulted in dramatic growth of the grafted neurons across the central nervous system of the rats, the treated animals did not show restoration of function in their forelimbs (hands). The researchers note that the human cells were still at a fairly early stage of development when function was tested, and that more time will likely be needed to be able to detect functional improvement.

Tuszynski went on to state, There are several important considerations that future studies will address. These include whether the extensive number of human axons make correct or incorrect connections; whether the new connections contain the appropriate chemical neurotransmitters to form functional connections; whether connections, once formed, are permanent or transient; and exactly how long it takes human cells to become mature. These considerations will determine how viable a candidate these cells might be for use in humans.

Lu, Tuszynski and their colleagues hope to identify the most promising neural stem cell type for repairing spinal cord injuries. Tuszynski emphasizes their commitment to a careful, methodical approach: Ultimately, we can only translate our animal studies into reliable human treatments by testing different neural stem cell types, carefully analyzing the results, and improving the procedure. We are encouraged, but we continue to work hard to rationally to identify the optimal cell type and procedural methods that can be safely and effectively used for human clinical trials.

1. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig ES, Havton LA, Zheng B, Conner JM, Marsala M, Tuszynski MH. Cell. 2012 Sep 14;150(6):1264-73

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Grafted Stem Cells Display Vigorous Growth in Spinal Cord Injury Model

While most are familiar with the potential for 3D printers to pump out plastic odds and ends for around the home, the technology also has far-reaching applications in the medical field. Research is already underway to develop 3D bioprinters able to create things as complex as human organs, and now engineering students in Canada have created a 3D printer that produces skin grafts for burn victims.

Called PrintAlive, the new machine was developed by University of Toronto engineering students Arianna McAllister and Lian Leng, who worked in collaboration with Professor Axel Guenther, Boyang Zhang and Dr. Marc Jeschke, the head of Sunnybrook Hospital's Ross Tilley Burn Centre.

While the traditional treatment for serious burns involves removing healthy skin from another part of the body so it can be grafted onto the affected area, the PrintAlive machine could put an end to such painful harvesting by printing large, continuous layers of tissue including hair follicles, sweat glands and other human skin complexities onto a hydrogel. Importantly, the device uses the patient's own cells, thereby eliminating the problem of the tissue being rejected by their immune system.

Because growing a culture of a patient's skin cells ready for grafting can typically take more than two weeks, the machine prints the patient's cells out in patterns of spots or stripes rather than a continuous sheet, to make them go further. The result is a cell-populated wound dressing that reproduces key features of human skin and can be precisely controlled in terms of thickness, structure and composition.

Having been under development since 2008, the team recently completed a second-generation, pre-commercial prototype that they say is smaller than an average microwave. This makes it portable enough to easily transport, which gives it the potential to one day revolutionize burn care in rural and developing areas around the world.

"Ninety per cent of burns occur in low and middle income countries, with greater mortality and morbidity due to poorly-equipped health care systems and inadequate access to burn care facilities," says Jeschke. "Regenerating skin using a patients own stem cells can significantly decrease the risk of death in developing countries."

So far, the 3D-printed skin grafts have been tested on mice, with the team planning to move onto pigs before clinical trials on humans in the next few years. They were recently named the Canadian winners in the 2014 James Dyson Awards, giving them US$3,500 to continue development and putting them in the running for the $60,000 main prize.

The PrintAlive bioprinter is detailed in the video below.

Sources: University of Toronto, James Dyson Award

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PrintAlive 3D bioprinter creates on-demand skin grafts for burn victims

TARPON SPRINGS --

A veterinarian in Tarpon Springs is doing research that could alleviate a problem thousands of dogs in Florida face.

Dr. Michael Amsberry is embarking on cutting edge research that could change the lives of those dogs and their owners.

Nube and Sage are part of a pilot study at Amsberrys Tarpon Springs pet care center.

Hes injecting dogs with stem cells to help with their Dermatitis, a condition that affects dogs in Florida each year.

Often times it starts out with skin thats irritated and red and then we often well suffer from secondary bacterial and yeast infections, said Dr. Michael Amsberry, Saint Francis Pet Care Center.

The treatment is inside a little jar that contains millions of stem cells that all come from one dogs umbilical cord in California. The treatment takes about 10 minutes, and the cells are in Amsberrys patients.

It is treating the body with the body not using chemicals or drugs.

There are drugs to treat dermatitis, and some of them work well. Amsberry and others like him said theyre looking for a cleaner, less expensive way.

The process to see if stem cell therapy actually works has only just begun.

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Tarpon vet using stem cells to treat doggie dermatitis

Company plans for the future of stem cell use

by Samantha Schmieder

Staff Writer

Next Healthcare Inc. of Germantown recently launched a partnership with Arizona Cardinals wide reciever Larry Fitzgerald to promote its newest venture, CelBank Pro to other professional athletes.

Next Healthcares CelBank is the collection of cell samples and storage of their blood, skin or stem cells to be used in the future. Stem cells are unspecialized cells that are able to renew themselves through cell division and can be scientifically manipulated to become another type of cell with a more specialized function. They offer hope to provide new ways to fight disease or injuries, according to the National Institutes of Health.

Essentially we are in the business of banking cells for people, Vin Singh, the founder and CEO of Next Healthcare, said.

While CelBank is geared toward anyone interested in using their own cells later in their life, CelBank Pro is geared toward sports players who are very likely to get injured or just worn down during their career.

Skin cells and stem cells are stored at a healthy time at someones life for later use in regenerative medicine, Singh said.

In 2006 and 2007, Singh, who lives in Boyds, heard about a method in Japan that was able to turn adult skin cells into stem cells. Singh decided to build Next Healthcare around these induced pluripotent stem cells, or iPS cells.

For me that was the real spark. I heard about that and thought, Wow, this is an amazing, revolutionary breakthrough, Singh said. Thats where the idea came from, what can we do with that technology. There has to be something that I can do for consumers to give them an advantage.

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Germantown

Company plans for the future of stem cell use

by Samantha Schmieder

Staff Writer

Next Healthcare Inc. of Germantown recently launched a partnership with Arizona Cardinals wide reciever Larry Fitzgerald to promote its newest venture, CelBank Pro to other professional athletes.

Next Healthcares CelBank is the collection of cell samples and storage of their blood, skin or stem cells to be used in the future. Stem cells are unspecialized cells that are able to renew themselves through cell division and can be scientifically manipulated to become another type of cell with a more specialized function. They offer hope to provide new ways to fight disease or injuries, according to the National Institutes of Health.

Essentially we are in the business of banking cells for people, Vin Singh, the founder and CEO of Next Healthcare, said.

While CelBank is geared toward anyone interested in using their own cells later in their life, CelBank Pro is geared toward sports players who are very likely to get injured or just worn down during their career.

Skin cells and stem cells are stored at a healthy time at someones life for later use in regenerative medicine, Singh said.

In 2006 and 2007, Singh, who lives in Boyds, heard about a method in Japan that was able to turn adult skin cells into stem cells. Singh decided to build Next Healthcare around these induced pluripotent stem cells, or iPS cells.

For me that was the real spark. I heard about that and thought, Wow, this is an amazing, revolutionary breakthrough, Singh said. Thats where the idea came from, what can we do with that technology. There has to be something that I can do for consumers to give them an advantage.

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Germantown's Next Healthcare pairs with NFL player

Edgar Irastorza was just 31 when his heart stopped beating in October 2008.

A Miami property manager, Irastorza had recently gained weight as his wife's third pregnancy progressed. "I kind of got pregnant, too," he said.

During a workout one day, he felt short of breath and insisted that friends rush him to the hospital. Minutes later, his pulse flatlined. He survived the heart attack, but the scar tissue that resulted cut his heart's pumping ability by a third. He couldn't pick up his children. He fell asleep every night wondering if he would wake up in the morning.

Desperation motivated Irastorza to volunteer for a highly unusual medical research trial: getting stem cells injected directly into his heart. "I just trusted my doctors and the science behind it, and said, 'This is my only chance,' " he said recently.

Over the last five years, by studying stem cells in lab dishes, test animals and intrepid patients like Irastorza, researchers have brought the vague, grandiose promises of stem cell therapies closer to reality.

Stem cells broke into the public consciousness in the early 1990s, alluring for their potential to help the body beat back diseases of degeneration like Alzheimer's, and to grow new parts to treat conditions like spinal cord injuries.

Progress has been slow. But researchers are learning how to best use stem cells, what types to use and how to deliver them to the body findings that are not singularly transformational, but progressive and pragmatic.

As many as 4,500 clinical trials involving stem cells are under way in the United States to treat patients with heart disease, blindness, Parkinson's, HIV, blood cancers and spinal cord injuries, among other conditions.

Initial studies suggest that stem cell therapy can be delivered safely, said Dr. Ellen Feigal, senior vice president of research and development at the California Institute of Regenerative Medicine, the state stem cell agency, which has awarded more than $2 billion toward stem cell research since 2006.

But enthusiasm for stem cells sometimes outstrips the science. When Gov. Rick Perry of Texas had adult stem cells injected into his spine in 2011 for a back injury, his surgeon had never tried the procedure and had no data to support the experiment. A June review in the New England Journal of Medicine found that "platelet-rich plasma" stem cell therapies praised by a number of athletes worked no better than placebos.

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Stem cell revolution gets closer

45 minutes ago Mesenchymal stem cell displaying typical ultrastructural characteristics. Credit: Robert M. Hunt/Wikipedia

Stem cells hold great promise as a means of repairing cells in conditions such as multiple sclerosis, stroke or injuries of the spinal cord because they have the ability to develop into almost any cell type. Now, new research shows that stem cell therapy can also work through a mechanism other than cell replacement.

In a study published today in Molecular Cell, a team of researchers led by the University of Cambridge has shown that stem cells "communicate" with cells by transferring molecules via fluid filled bags called vesicles, helping other cells to modify the damaging immune response around them.

Although scientists have speculated that stem cells might act rather like drugs in sensing signals, moving to specific areas of the body and executing complex reactions this is the first time that a molecular mechanism for this process has been demonstrated. By understanding this process better, researchers can identify ways of maximising the efficiency of stem-cell-based therapies.

Dr Stefano Pluchino from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, who led the study, said: "These tiny vesicles in stem cells contain molecules like proteins and nucleic acids that stimulate the target cells and help them to survive they act like mini "first aid kits".

"Essentially, they mirror how the stem cells respond to an inflammatory environment like that seen during complex neural injuries and diseases, and they pass this ability on to the target cells. We think this helps injured brain cells to repair themselves."

Mice with damage to brain cells such as the damage seen in multiple sclerosis show a remarkable level of recovery when neural stem/precursor cells (NPCs) are injected into their circulatory system. It has been suggested that this happens because the NPCs discharge molecules that regulate the immune system and that ultimately reduce tissue damage or enhance tissue repair.

The team of researchers from the UK, Australia, Italy, China and Spain has now shown that NPCs make vesicles when they are in the vicinity of an immune response, and especially in response to a small protein, or cytokine, called Interferon-gamma which is released by immune cells. This protein has the ability to regulate both the immune responses and intrinsic brain repair programmes and can alter the function of cells by regulating the activity of scores of genes.

Their results show that a highly specific pathway of gene activation is triggered in NPCs by IFN-gamma, and that this protein also binds to a receptor on the surface of vesicles. When the vesicles are released by the NPCs, they adhere and are taken up by target cells. Not only does the target cell receive proteins and nucleic acids that can help them self-repair, but it also receives the IFN-gamma on the surface of the vesicles, which activates genes within the target cells.

The researchers, who were funded by the European Research Council and the Italian MS Society, used electron microscopy and superresolution imaging to visualise the vesicles moving between the NPCs and target cells in vitro.

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Stem cells use 'first aid kits' to repair damage

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Newswise NEW YORK, September 18, 2014 Scientists at NYU Langone Medical Center have found a way to boost dramatically the efficiency of the process for turning adult cells into so-called pluripotent stem cells by combining three well-known compounds, including vitamin C.

Using the new technique in mice, the researchers increased the number of stem cells obtained from adult skin cells by more than 20-fold compared with the standard method. They say their technique is efficient and reliable, and thus should generally accelerate research aimed at using stem cells to generate virtually any tissue. Stem cells are immature or uncommitted cells that are theoretically capable of becoming any cell type.

This big boost in efficiency gives us an opportunity now to study stem cell programming mechanisms at high resolution, says Matthias Stadtfeld, PhD, assistant professor of cell biology and a member of the Skirball Institute of Biomolecular Medicine and the Helen L. and Martin S. Kimmel Center for Stem Cell Biology at NYU Langone Medical Center, who led the research.

This is a very exciting advance, says Ruth Lehmann, PhD, director of the Kimmel Center for Stem Cell Biology and the Skirball Institute at NYU Langone and chair of the Department of Cell Biology. The new technology developed by the Stadtfeld lab to reprogram differentiated cells efficiently and effectively brings the prospect of stem cell technology for safe use in regenerative medicine ever so much closer."

The standard method for reprogramming skin, blood, or other tissue-specific cell types into induced pluripotent stem cells (iPSCs) was reported in 2006 by the laboratory of Kyoto Universitys Shinya Yamanaka, who later won a Nobel Prize for the achievement. The method involves the artificial expression of four key genes dubbed OKSM (for Oct4, Klf4, Sox2 and myc) whose collective activity slowly prods cells into an immature state much like that of an early embryonic cell.

In principle, one could take a sample of cells from a person, induce the cells to become iPSCs, then multiply the iPSCs in a lab dish and stimulate them to mature towards desired adult cell types such as blood, brain or heartwhich then could be used to replace injured or diseased tissue in that same individual.

But there are many formidable technical obstacles, among which is the low efficiency of currently used protocols. Converting most cell types into stable iPSCs occurs at rates of 1 percent or less, and the process can take weeks.

Researchers throughout the world have been searching for ways to boost this efficiency, and in some cases have reported significant gains. These procedures, however, often alter vital cellular genes, which may cause problems for potential therapies. For the new study, reported online today in Stem Cell Reports, Dr. Stadtfeld and his laboratory team decided to take a less invasive approach and investigate chemical compounds that transiently modulate enzymes that are present in most cells. We especially wanted to know if these compounds could be combined to obtain stem cells at high efficiency, Dr. Stadtfeld says.

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NYU Langone Scientists Report Reliable and Highly Efficient Method for Making Stem Cells

45 minutes ago A new method resulted in a colony of stem cells, glowing green, derived from one adult immune cell. Credit: Laboratory of Matthias Stadtfeld at NYU Langone Medical center

Scientists at NYU Langone Medical Center have found a way to boost dramatically the efficiency of the process for turning adult cells into so-called pluripotent stem cells by combining three well-known compounds, including vitamin C. Using the new technique in mice, the researchers increased the number of stem cells obtained from adult skin cells by more than 20-fold compared with the standard method. They say their technique is efficient and reliable, and thus should generally accelerate research aimed at using stem cells to generate virtually any tissue. Stem cells are immature or uncommitted cells that are theoretically capable of becoming any cell type.

"This big boost in efficiency gives us an opportunity now to study stem cell programming mechanisms at high resolution," says Matthias Stadtfeld, PhD, assistant professor of cell biology and a member of the Skirball Institute of Biomolecular Medicine and the Helen L. and Martin S. Kimmel Center for Stem Cell Biology at NYU Langone Medical Center, who led the research.

"This is a very exciting advance," says Ruth Lehmann, PhD, director of the Kimmel Center for Stem Cell Biology and the Skirball Institute at NYU Langone and chair of the Department of Cell Biology. "The new technology developed by the Stadtfeld lab to reprogram differentiated cells efficiently and effectively brings the prospect of stem cell technology for safe use in regenerative medicine ever so much closer."

The standard method for reprogramming skin, blood, or other tissue-specific cell types into "induced pluripotent stem cells" (iPSCs) was reported in 2006 by the laboratory of Kyoto University's Shinya Yamanaka, who later won a Nobel Prize for the achievement. The method involves the artificial expression of four key genes dubbed OKSM (for Oct4, Klf4, Sox2 and myc) whose collective activity slowly prods cells into an immature state much like that of an early embryonic cell.

In principle, one could take a sample of cells from a person, induce the cells to become iPSCs, then multiply the iPSCs in a lab dish and stimulate them to mature towards desired adult cell types such as blood, brain or heartwhich then could be used to replace injured or diseased tissue in that same individual.

But there are many formidable technical obstacles, among which is the low efficiency of currently used protocols. Converting most cell types into stable iPSCs occurs at rates of 1 percent or less, and the process can take weeks.

Researchers throughout the world have been searching for ways to boost this efficiency, and in some cases have reported significant gains. These procedures, however, often alter vital cellular genes, which may cause problems for potential therapies. For the new study, reported online today in Stem Cell Reports, Dr. Stadtfeld and his laboratory team decided to take a less invasive approach and investigate chemical compounds that transiently modulate enzymes that are present in most cells. "We especially wanted to know if these compounds could be combined to obtain stem cells at high efficiency," Dr. Stadtfeld says.

Two of these compounds influence well known signaling pathways, called Wnt and TGF-, which regulate multiple growth-related processes in cells. The third is vitamin C (also known as ascorbic acid). Best known as a powerful antioxidant, the vitamin was recently discovered to assist in iPSC induction by activating enzymes that remodel chromatinthe spiral scaffold for DNAto regulate gene expression.

Simon Vidal, a graduate student in the Stadtfeld lab, and Bhishma Amlani, a postdoctoral researcher, looked first at mouse skin fibroblasts, the most common cell type used for iPSC research. Adding to fibroblasts engineered to express OKSM either vitamin C, a compound to activate Wnt signaling, or a compound to inhibit TGF- signaling increased iPSC-induction efficiency weakly to about 1% after a week of cell culture. Combining any two worked a bit better. But combining all three brought the efficiency to about 80 percent in the same period of time.

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Team reports reliable, highly efficient method for making stem cells

PUBLIC RELEASE DATE:

12-Sep-2014

Contact: Peggy Murphy pemurphy@luriechildrens.org 773-755-7485 Children's Memorial Hospital

Metastatic melanoma is a highly aggressive skin cancer whose incidence is on the rise at an alarming rate. Research has revealed that metastatic tumor cells share similar signaling pathways with embryonic stem cells to sustain plasticity and growth. However, major regulators of these pathways are often missing in tumor cells, thus allowing uncontrolled tumor growth and spreading to occur.

During early vertebrate development, Nodal, an embryonic growth factor that governs the growth, pattern and position of tissues, is critical for normal maturation. Nodal plays a significant role in maintaining the pluripotency of embryonic stem cells, meaning the ability of stem cells to differentiate into any of the three germ layers that comprise the body. The recent discovery of Nodal's re-expression in several aggressive and metastatic cancers has highlighted its critical role in self-renewal and maintenance of the stem cell-like characteristics of tumor cells such as melanoma. However, the signaling pathway receptors utilized by melanoma cells to propagate Nodal's effect remain(s) mostly anecdotal and unexplored.

The laboratory of Mary J.C. Hendrix, PhD made the novel discovery that embryonic stem cells and metastatic melanoma cells share a similar repertoire of receptors known as Type I serine/threonine kinase(s), but diverge in their Type II receptor expression. Further testing indicated that metastatic melanoma cells and embryonic stem cells use different receptors for Nodal signal transduction. These findings reveal the divergence in Nodal signaling between embryonic stem cells and metastatic melanoma that can impact new therapeutic strategies targeting the re-emergence of embryonic pathways in cancer.

This work is published in the International Journal of Cancer. Mary J.C. Hendrix, PhD points out: "Nodal-expressing tumor cells don't respond favorably to conventional therapies, supporting the premise that a combinatorial approach to targeting Nodal subpopulations within tumors, along with a front-line therapy, would constitute a more rational approach for treating aggressive cancer". Zhila Khalkhali-Ellis, PhD, senior research scientist in the Hendrix laboratory and the lead author says: "Our discoveries are important for advanced stage aggressive melanoma. Given that limited therapeutic options are currently available for this cancer, we have the opportunity to investigate whether the receptors can be modulated so that the signaling molecule can be neutralized to decrease aggressive behavior." The research was supported by the National Institutes of Health.

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Zhila Khalkhali-Ellis, PhD is Research Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine; and a member of the Cancer Biology and Epigenomics Program of Stanley Manne Children's Research Institute, affiliated with Ann & Robert H. Lurie Children's Hospital of Chicago.

Mary J.C. Hendrix, PhD is President & Scientific Director of Manne Research Institute; Children's Research Fund Professor; William G. Swartchild, Jr. Distinguished Research Professor at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

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Re-expression of an embryonic signaling pathway in Melanoma utilizes different receptors

St. Petersburg, FL (PRWEB) September 16, 2014

Aging skin inevitably wrinkles, thins and sags.

The main internal reason for this is loss of collagen production. By age 60, skin has 45% less collagen than it did when young due to this slow down. Collagen holds up skin structure.

In order to maintain healthy, beautiful skin, collagen production should be boosted. There are several ways to do this, but the relatively new scientific approach is through use of stem cells (non-embryonic).

"The cost is higher than other types of serums, but you also get what you pay for," says Kathy Heshelow, founder of Sublime Beauty."Stem cell serums rich in growth factors and human fibroblast conditioned media bring back firmer, younger and smoother skin."

Scientists have used these ingredients in wound repair with great success, and the crossover to skin care seemed natural. TGF-b or Transforming Growth Factor-beta is considered to be one of the most important growth factors to stimulate collagen production, promote synthesis and inhibit thinning of skin.

The Sublime Beauty serum, Cell Renewal | Fibroblast Serum, contains these very growth factors. A brochure explaining more about the ingredients is available on the product page of the company webstore.

Similar serums on the market are far more expensive the one offered by Sublime Beauty. Take 25% Off the stem cell serum at Amazon with coupon code FIBRO52V now.

ABOUT: Sublime Beauty is a quality skincare company that focuses on products to Age Younger. Ingredients help to boost collagen, hydrate, relax wrinkles and improve skin. A niche includes healthy Skin Brushes. The company webstore offers free standard shipping and a VIP Club. Sign up for Secret Sales on the site. Products also available on Amazon.

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A Superior Way to Make Skin Younger and Assure Continual Collagen Production, from Sublime Beauty

Surgeons implanted retinal tissue created after reverting the patient's own cells to a "pluripotent" state

Researchers were able to grow sheets of retinal tissue from induced pluripotent stem cells, and have now implanted them for the first time in a patient. Credit: RIKEN/Foundation for Biomedical Research and Innovation

A Japanese woman in her 70s is the world's first recipient of cells derived from induced pluripotent stem cells, a technology that has created great expectations since it could offer the same advantages as embryo-derived cells but without some of the controversial aspects and safety concerns.

In a two-hour procedure starting at 14:20 local time today, a team of three eye specialists lead by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, transplanted a 1.3 by 3.0 millimeter sheet of retinal pigment epithelium cells into an eye of the Hyogo prefecture resident, who suffers from age-related macular degeneration.

The procedure took place at the Institute of Biomedical Research and Innovation Hospital, next to the RIKEN Center for Developmental Biology (CDB) where ophthalmologist Masayo Takahashi had developed and tested the epithelium sheets. She derived them from the patient's skin cells, after producing induced pluripotent stem (iPS) cells and then getting them to differentiate into retinal cells.

Afterwards, the patient experienced no effusive bleeding or other serious problems, RIKEN has reported.

The patient took on all the risk that go with the treatment as well as the surgery, Kurimoto said in a statement released by RIKEN. I have deep respect for bravery she showed in resolving to go through with it.

He hit a somber note in thankingYoshiki Sasai, a CDB researcher who recenty committed suicide. This project could not have existed without the late Yoshiki Sasais research, which led the way to differentiating retinal tissue from stem cells.

Kurimoto also thanked Shinya Yamanaka, a stem-cell scientist at Kyoto University without whose discovery of iPS cells, this clinical research would not be possible. Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for that work.

Kurimoto performed the procedure a mere four days after a health-ministry committee gave Takahashi clearance for the human trials (see 'Next-generation stem cells cleared for human trial').

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Next-Generation Stem Cells Transplanted in Human for the First Time

Researchers at EMBL-EBI have resolved a long-standing challenge in stem cell biology by successfully 'resetting' human pluripotent stem cells to a fully pristine state, at point of their greatest developmental potential. The study, published in Cell, involved scientists from the UK, Germany and Japan and was led jointly by EMBL-EBI and the University of Cambridge.

Embryonic stem (ES) cells, which originate in early development, are capable of differentiating into any type of cell. Until now, scientists have only been able to revert 'adult' human cells (for example, liver, lung or skin) into pluripotent stem cells with slightly different properties that predispose them to becoming cells of certain types. Authentic ES cells have only been derived from mice and rats.

"Reverting mouse cells to a completely 'blank slate' has become routine, but generating equivalent nave human cell lines has proven far more challenging," says Dr Paul Bertone, Research Group Leader at EMBL-EBI and a senior author on the study. "Human pluripotent cells resemble a cell type that appears slightly later in mammalian development, after the embryo has implanted in the uterus."

At this point, subtle changes in gene expression begin to influence the cells, which are then considered 'primed' towards a particular lineage. Although pluripotent human cells can be cultured from in vitro fertilised (IVF) embryos, until now there have been no human cells comparable to those obtained from the mouse.

Wiping cell memory

"For years, it was thought that we could be missing the developmental window when nave human cells could be captured, or that the right growth conditions hadn't been found," Paul explains. "But with the advent of iPS cell technologies, it should have been possible to drive specialised human cells back to an earlier state, regardless of their origin -- if that state existed in primates."

Taking a new approach, the scientists used reprogramming methods to express two different genes, NANOG and KLF2, which reset the cells. They then maintained the cells indefinitely by inhibiting specific biological pathways. The resulting cells are capable of differentiating into any adult cell type, and are genetically normal.

The experimental work was conducted hand-in-hand with computational analysis.

"We needed to understand where these cells lie in the spectrum of the human and mouse pluripotent cells that have already been produced," explains Paul. "We worked with the EMBL Genomics Core Facility to produce comprehensive transcriptional data for all the conditions we explored. We could then compare reset human cells to genuine mouse ES cells, and indeed we found they shared many similarities."

Together with Professor Wolf Reik at the Babraham Institute, the researchers also showed that DNA methylation (biochemical marks that influence gene expression) was erased over much of the genome, indicating that reset cells are not restricted in the cell types they can produce. In this more permissive state, the cells no longer retain the memory of their previous lineages and revert to a blank slate with unrestricted potential to become any adult cell.

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Scientists revert human stem cells to pristine state

San Diego scientists have taken a neurochemical fingerprint of schizophrenia. And they did it without probing the brains of lab mice.

UC San Diego's Vivian Hook, first author of a paper published Thursday in Stem Cell Reports, says mice just wouldn't cut it for her research on schizophrenia.

"The basic reason I didn't do it in mice is because mice naturally don't get schizophrenia," Hook said.

Hook and her colleagues tried a fairly new approach. They took skin cells from three schizophrenia patients, converted them into stem cells, and then turned those stem cells into brain cells. They ended up with tiny brain fragments in a dish, which mirrored the cells inside the actual brains of those human patients.

"We found that the schizophrenic neurons showed aberrant increases in certain neurotransmitters. The cells were pumping out more dopamine, norepinephrine and epinephrine than non-schizophrenic brain cells," Hook said. "There's a chemical imbalance that has been predicted in schizophrenia, and these model schizophrenic-derived nerve cells provide data showing that."

Hook says the study also proves that stem-cell derived neurons can secrete neurotransmitters, just like cells in living human brains. That could open up research into new drugs for schizophrenia, and could potentially help answer longstanding questions about conditions like autism, ALS and Alzheimer's.

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Stem Cells Give San Diego Scientists Useful Portrait Of Schizophrenia

TOKYO: Japanese researchers on Friday (Sep 12) conducted the world's first surgery to implant "iPS" stem cells in a human body in a major boost to regenerative medicine, two institutions involved said.

A female patient in her 70s with age-related macular degeneration (AMD), a common medical condition that can lead to blindness in older people, had a sheet of retina cells that had been created from iPS cells implanted. "It is the first time in the world that iPS cells have been transplanted into a human body," a spokeswoman for Riken, one of the research institutions, told AFP.

The research team used induced Pluripotent Stem (iPS) cells - which have the potential to develop into any cell in the body - that had originally come from the skin of the patient. Until the discovery of iPS several years ago, the only way to obtain stem cells was to harvest them from human embryos.

"We feel very much relieved," ophthalmologist Masayo Takahashi, the leader of the project at Riken, told a news conference after the surgery in Kobe. "We want to take it as a big step forward. But we must go on and on from here."

In a statement, the institution said that "no serious adverse phenomena such as excessive bleeding occurred" during the two-hour procedure. The surgery is still at an experimental stage, but if it is successful, doctors hope it will stop the deterioration in vision that comes with AMD.

The patient - one of six expected to take part in the trial - will be monitored over the next four years to determine how well the implants have performed, whether the body has accepted them and if they have become cancerous.

AMD, a condition that is incurable at present, affects mostly middle-aged and older people and can lead to blindness. It afflicts around 700,000 people in Japan alone.

The study was being carried out by researchers from government-backed research institution Riken and the Institute of Biomedical Research and Innovation Hospital.

Stem cell research is a pioneering field that has excited many in the scientific community with the potential they believe it offers. Stem cells are infant cells that can develop into any part of the body. Harvesting from human embryos is controversial because it requires the destruction of the embryo, a process to which religious conservatives, among others, object.

Groundbreaking work done in 2006 by Shinya Yamanaka at Kyoto University, a Nobel Laureate in medicine last year, succeeded in generating stem cells from adult skin tissue.

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Japan carries out first iPS stem cell retina surgery

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Newswise LA JOLLAFor the first time, scientists have turned human skin cells into transplantable white blood cells, soldiers of the immune system that fight infections and invaders. The work, done at the Salk Institute, could let researchers create therapies that introduce into the body new white blood cells capable of attacking diseased or cancerous cells or augmenting immune responses against other disorders.

The work, as detailed in the journal Stem Cells, shows that only a bit of creative manipulation is needed to turn skin cells into human white blood cells.

"The process is quick and safe in mice," says senior author Juan Carlos Izpisua Belmonte, holder of Salk's Roger Guillemin Chair. "It circumvents long-standing obstacles that have plagued the reprogramming of human cells for therapeutic and regenerative purposes."

Those problems includes the long timeat least two monthsand tedious laboratory work it takes to produce, characterize and differentiate induced pluripotent stem (iPS) cells, a method commonly used to grow new types of cells. Blood cells derived from iPS cells also have other obstacles: an inability to engraft into organs or bone marrow and a likelihood of developing tumors.

The new method takes just two weeks, does not produce tumors, and engrafts well.

"We tell skin cells to forget what they are and become what we tell them to bein this case, white blood cells," says one of the first authors and Salk researcher Ignacio Sancho-Martinez. "Only two biological molecules are needed to induce such cellular memory loss and to direct a new cell fate."

Belmonte's team developed the faster technique (called indirect lineage conversion) and previously demonstrated that these approaches could be used to produce human vascular cells, the ones that line blood vessels. Rather than reversing cells all the way back to a stem cell state before prompting them to turn into something else, such as in the case of iPS cells, the researchers "rewind" skin cells just enough to instruct them to form the more than 200 cell types that constitute the human body.

The technique demonstrated in this study uses a molecule called SOX2 to become somewhat plasticthe stage of losing their "memory" of being a specific cell type. Then, researchers use a genetic factor called miRNA125b that tells the cells that they are actually white blood cells.

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Simple Method Turns Human Skin Cells Into Immune-Fighting White Blood Cells

Dr. Aivee Teos newest clinic combines multi-faceted skin typing with essential treatments to get The Aivee Glow

August 28, 2014The Aivee Clinic officially launches at the SM Mega Fashion Hall. After five years since opening her posh clinic at the Fort, Dr. Aivee Teo elevates her passion for advanced skin care technology and anti-aging treatments with the new clinic concept, The Aivee Clinic. The beauty hub couldnt have been in a better locationstationed alongside global fashion brands. Dr. Aivee Teo, one of the countrys most sought after dermatologists, after all, has as much passion for beauty as she has for fashion. Her success in the business of skin care is widely known, and as a fashion lover, she has constantly been on best-dressed lists. Beauty and fashion truly go hand in hand.

What started out as a practice in the pursuit of beauty, one that thrived purely on word of mouth, has inevitably made Dr. Aivee as one of the major players in the industry. Getting healthy, blemish-free, and luminous skin using non-invasive or minimally invasive methods has always been her technique. And she continues to push the standards with a full integration of beauty and wellness with The Aivee Group.

AIVEE LEAGUE

What is The Aivee Glow? Its a signature look defined as a luminous, radiant, and natural beauty that transcends external perfection. With the new clinic, Dr. Aivee strengthens the four pillars of The Aivee Group: The Aivee Institute (first class center for advanced dermatology, cosmetic surgery, hair restoration, and aesthetic stem cell therapy), Stemcare Institute (premiere center for pain and regenerative medicine using fat stem cells), Aivee Skin Science (research center for developing cosmeceutical and nutriceutical products) and now, The Aivee Clinic (skin-focused approach for no-downtime treatments). The Aivee Group is one well-oiled machine, with all its parts complementing each other toward a holistic beauty goal.

GRADE A

Its no secret that the husband and wife partnership of Dr. Z and Aivee Teo, their love and commitment for each other and their field, has brought them happiness and success. From surviving a long-distance relationship, shuffling back and forth Manila and Singapore to attend to their respective clinics, and always pursuing new ways to rejuvenate skin and provide a sense of well-being. All this while keeping their children close by and rarely being separate from each other. And if youve ever had the privilege of interviewing them together, they really finish each others sentences. Whether thats about their practice or about how they commit to make everything work for their family and business.

This dynamic duo established their anti-aging institute over a decade ago, utilizing maintenance procedures, non-invasive lasers, cutting edge technology such as stem cell therapy and liquid face lifts, and cosmetic surgery. The awareness of the growing needs of their patients and their recent travels to the US and Europe brought them to a new realization. With patients requesting for dramatic makeover programs, twice-a-year rejuvenation therapies and innovative treatments with the least amount or no downtime, SmartSkin became the clear answer as the way to move forward.

The SmartSkin Typing concept is a multi-faceted system with a digital tailor-made evaluation of the skin. By assessing and categorizing skin as oily or dry, sensitive or resistant, pigmented or non-pigmented, wrinkled or tight, you come up with a very specific skin type. From this, a highly customized skin treatment can easily be made. In keeping with the holistic approach, skin experts at The Aivee Clinic can then set the appropriate treatment programprocedures, health supplements, and skin careto achieve that healthy glow.

SKIN TECH

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Babraham Institute scientists, in collaboration with colleagues at the Cambridge Stem Cell Institute and the European Bioinformatics Institute, have published findings today in the journal Cell giving hope that researchers will be able to generate base-state, nave human stem cells for future medical applications. The study demonstrates that human stem cells can be reverted back to a base state, losing characteristics that mark them as belonging to a specific cell lineage and instead regaining the identify of a non-specialised cells with unrestricted potential (pluripotency) to develop into any cell type.

The study's lead researchers, based at the Wellcome Trust-Medical Research Council Stem Cell Institute in Cambridge, reset human stem cells back to a pluripotent state. Previous work in mice had described the characteristics of base-state mouse stem cells and the group were able to show that these characteristics were largely shared by reset human pluripotent stem cells, giving confirmation that these human cells were indeed reverted to a nave state.

Part of this analysis involved looking at the epigenetic regulation in the base-state human stem cells. This analysis was performed by Dr Gabriella Ficz, Professor Wolf Reik and their colleagues at the BBSRC-supported Babraham Institute, Cambridge, UK. Epigenetics refers to the range of DNA modifications that affect gene expression but are not sequence-based. For example, chemical methyl tags on DNA can silence gene expression. Cells gain epigenetic markers as they assume a defined cell identify. Therefore, early embryo cells show a low level of methylation, corresponding to their lack of commitment to a particular cell fate. Last year, the Babraham group discovered a large-scale loss of methylation from the genome of reset mouse embryonic stem cells.

Ficz and Reik were able to show that, overall, the reset human stem cells showed a loss of methylation marks throughout the genome; they essentially had their epigenetic memories wiped clean. This low level of DNA methylation demonstrated their similarity to early embryonic cells and thus was a strong indication of their regained pluripotency.

Dr Gabriella Ficz, who undertook the epigenetic analysis of the cells as a post-doctoral researcher in Professor Reik's group, said: "This study brings us one step closer to the ultimate aim in regenerative medicine of using patient-derived cells to avoid immune rejection in cell and organ replacement therapies. It's all about finding out what the cell needs in order to survive and multiply while making sure that they have lost the memory of the tissue they came from. Both conditions need to be fulfilled for successful use of embryonic stem cells in tissue generation."

Professor Wolf Reik, Group Leader at the Babraham Institute continued: "We can liken this reprogramming to giving cells amnesia so they forget any previous developmental decisions they have made. Returning them to this state means that we can then control their cellular decisions, allowing us to generate the particular types of cells needed. This area has huge medical potential, for example, being able to provide reset stem cells back to a patient that we can be confident will develop into the correct cell type as required, for example, nerve cells."

Professor Michael Wakelam, Director of the Babraham Institute added: "This research is an enormous step forward in answering questions about whether human stem cells can be reset to a ground state and the feasibility of maintaining pluripotency. It is also an excellent demonstration of the importance of collaborative research making the most of the extensive and complementary expertise that can be found in Cambridge."

The Babraham Institute's research contribution to this study was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust.

Explore further: New technique maps life's effects on our DNA

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Wiping the slate clean: Erasing cellular memory and resetting human stem cells

Father-of-two James Cross, 55, suffered a heart attack in February Surgeons at the London Chest Hospital offered him a unique chance Experimental therapy involved injecting stem cells from Mr Cross's hip into his heart in the hope they would encourage the organ to repair itself It appears to have worked as Mr Cross's heart muscle function has increased from 21% after the attack to 37% and it is still improving Experts hope the new technique will increase survival rates by a quarter

By John Naish

Published: 20:38 EST, 8 September 2014 | Updated: 07:12 EST, 9 September 2014

James Cross, 55,was offered experimental treatment after suffering a heart attack in February

After James Cross had a heart attack in February, he was given a unique chance for a new life.

Surgeons at the London Chest Hospital offered the 55-year-old experimental therapy that involved injecting his own stem cells into the damaged organ.

This was done in the hope that it would encourage his heart to repair itself.

The injected stem cells should prevent the hearts muscle tissue from becoming increasingly damaged after suffering a lack of oxygen during the heart attack.

And it seems to have worked.

After the heart attack, I had 21 per cent of my heart muscle functioning, as opposed to the normal 61 per cent, says James.

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Could stem cells from your hip repair your heart after an attack?

Aging News & Information

Aging Muscles May Be Restored by Discovery of a Key to Making Muscle

Results hailed as important step toward developing new muscle to treat muscle diseases; good news for seniors with muscles wasting away from aging

Sept. 8, 2014 Promising results have been achieved in repairing damaged tissue in muscles which could lead to a new therapeutic approach to treating the millions of people suffering from muscle diseases, including those with muscular dystrophies and muscle wasting associated with cancer and aging seniors, according to the study, published September 7 in Nature Medicine.

Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) in La Jolla, California, have developed this novel technique to promote tissue repair in damaged muscles. The technique also creates a sustainable pool of muscle stem cells needed to support multiple rounds of muscle repair.

There are two important processes that need to happen to maintain skeletal-muscle health. First, when muscle is damaged by injury or degenerative disease such as muscular dystrophy, muscle stem cellsor satellite cellsneed to differentiate into mature muscle cells to repair injured muscles.

Second, the pool of satellite cells needs to be replenished so there is a supply to repair muscle in case of future injuries. In the case of muscular dystrophy, the chronic cycles of muscle regeneration and degeneration that involve satellite-cell activation exhaust the muscle stem-cell pool to the point of no return.

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Aging Muscles May Be Restored by Discovery of a Key to Making Muscle

Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have developed a novel technique to promote tissue repair in damaged muscles. The technique also creates a sustainable pool of muscle stem cells needed to support multiple rounds of muscle repair. The study, published September 7 in Nature Medicine, provides promise for a new therapeutic approach to treating the millions of people suffering from muscle diseases, including those with muscular dystrophies and muscle wasting associated with cancer and aging.

There are two important processes that need to happen to maintain skeletal-muscle health. First, when muscle is damaged by injury or degenerative disease such as muscular dystrophy, muscle stem cells -- or satellite cells -- need to differentiate into mature muscle cells to repair injured muscles. Second, the pool of satellite cells needs to be replenished so there is a supply to repair muscle in case of future injuries. In the case of muscular dystrophy, the chronic cycles of muscle regeneration and degeneration that involve satellite-cell activation exhaust the muscle stem-cell pool to the point of no return.

"Our study found that by introducing an inhibitor of the STAT3 protein in repeated cycles, we could alternately replenish the pool of satellite cells and promote their differentiation into muscle fibers," said Alessandra Sacco, Ph.D., assistant professor in the Development, Aging, and Regeneration Program at Sanford-Burnham. "Our results are important because the process works in mice and in human muscle cells."

"Our next step is to see how long we can extend the cycling pattern, and test some of the STAT3 inhibitors currently in clinical trials for other indications such as cancer, as this could accelerate testing in humans," added Sacco.

"These findings are very encouraging. Currently, there is no cure to stop or reverse any form of muscle-wasting disorders -- only medication and therapy that can slow the process," said Vittorio Sartorelli, M.D., chief of the Laboratory of Muscle Stem Cells and Gene Regulation and deputy scientific director at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). "A treatment approach consisting of cyclic bursts of STAT3 inhibitors could potentially restore muscle mass and function in patients, and this would be a very significant breakthrough."

Revealing the mechanism of STAT3

STAT3 (signal transducer and activator of transcription 3) is a protein that activates the transcription of genes in response to IL-6, a signaling protein released by cells in response to injury and inflammation. Prior to the study, scientists knew that STAT3 played a complex role in skeletal muscle, promoting tissue repair in some instances and hindering it in others. But the precise mechanism of how STAT3 worked was a mystery.

The research team first used normally aged mice and mice models of a form of muscular dystrophy that resembles the human disease to see what would happen if they were given a drug to inhibit STAT3. They found that the inhibitor initially promoted satellite-cell replication, followed by differentiation of the satellite cells into muscle fibers. When they injected the STAT3 inhibitor every seven days for 28 days, they found an overall improvement in skeletal-muscle repair, and an increase in the size of muscle fibers.

"We were pleased to find that we achieved similar results when we performed the experiments in human muscle cells," said Sacco. "We have discovered that by timing the inhibition of STAT3 -- like an "on/off" light switch -- we can transiently expand the satellite-cell population followed by their differentiation into mature muscle cells."

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Researchers discover key to making new muscles

(PRWEB) September 08, 2014

In 2012, minence Organic Skin Care redefined anti-aging skin care with the launch of their Age Corrective Collection. Today, minence is revolutionizing the skin care industry with two new products and an all-inclusive Starter Set that will complete the anti-aging line. The Monoi Age Corrective Exfoliating Cleanser, Bamboo Age Corrective Masque and Age Corrective Starter Set will be available to purchase at select spas and salons worldwide as of September 5, 2014.

Aging skin impacts everyone eventually. Regardless of whether it is fine lines or crows feet, most people want to take steps to correct them. Some go to drastic lengths and often look to synthetic skin care solutions to regain their youthful appearance, but this is no longer necessary because minence has the ultimate Age Corrective Routine that is just as results-oriented, and its all natural and organic.

Repair aging skin naturally by using each of the Age Corrective products in minences easy-to-follow skin care routine with seven unique steps. A complexion that looks, and acts, completely ageless is simple and easy with featured botanical actives such as Natural Retinol Alternative and PhytoCellTec Swiss Green Apple Stem Cell Technology specially formulated to erase the signs of aging skin. The Natural Retinol Alternative contains chicory root and tara tree which mimics and out-performs conventional retinol. Plus, the addition of Swiss Green Apple Stem Cells delivers an increase in cell regeneration and longevity to provide incredible results:

As one of our most popular collections, our Age Corrective products are continuously hitting our top 10 best sellers list. Due to widespread demand, and in order to make it easier for consumers and spa partners to capture the true benefits of a complete Age Corrective Routine, we are introducing two new products to the collection, says Boldijarre Koronczay, President of minence Organic Skin Care. Each product in the collection harnesses the anti-aging power of our exclusive Natural Retinol Alternative and PhytoCellTec Swiss Green Apple Stem Cell Technology. The new masque offers the additional benefits of our Anti-Aging Stem Cell Complex to reduce wrinkle depth by 26%. These advanced anti-aging actives will erase and repair the signs of aging and when all the products are used in conjunction, the results are astounding!

For more information, images and sample requests please contact Elisa Kosonen at ekosonen(at)eminenceorganics(dot)com or 1.604.505.3103.

About minence Organic Skin Care

minence Organic Skin Care is the award-winning provider of the most effective skin care products in the natural and organic skin care industry. With more than half a century of herbal craftsmanship and innovation, and several centuries of unsurpassed skin rejuvenation techniques unique to Hungary, they offer the highest quality natural skin care to leading salons, spas and their clients in more than 40 countries around the world. minences superior spa treatments and products rely on a unique combination of hand-picked fresh ingredients. Vitamins are captured in their all-natural fresh base, offering dramatic results as actual seeds, pulps and peels begin the regenerative and healing powers that only nature can produce. Voted Favorite Skin Care Line by spa professionals and seen as Hollywoods skin care secret, with devoted fans such as Madonna, Jessica Biel, Katherine Heigl, Jena Malone and Mark Ruffalo, minence is renowned for premium organic and Biodyanmic skin care that enhances your well-being naturally. A commitment to the environment is integral to their business practices and they strive to create products that are good for the earth as well as good for the skin. By enlisting wind and solar power energy in the making of products, recyclable packaging with vegetable-based inks, geothermal heating in the laboratory and an eco-alternative design of the head office, minence does all that they can to combat climate change. Starting in the fall of 2012, the Forests for the Future initiative brought that commitment to the environment to a whole new level by planting a tree for every product sold. Visit http://www.eminenceorganics.com for more information.

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minence Organic Skin Care Adds New Products to Complete their Most Advanced Anti-Aging Skin Care Line

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Newswise La Jolla, Calif., September 7, 2014Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have developed a novel technique to promote tissue repair in damaged muscles. The technique also creates a sustainable pool of muscle stem cells needed to support multiple rounds of muscle repair. The study, published September 7 in Nature Medicine, provides promise for a new therapeutic approach to treating the millions of people suffering from muscle diseases, including those with muscular dystrophies and muscle wasting associated with cancer and aging.

There are two important processes that need to happen to maintain skeletal-muscle health. First, when muscle is damaged by injury or degenerative disease such as muscular dystrophy, muscle stem cellsor satellite cellsneed to differentiate into mature muscle cells to repair injured muscles. Second, the pool of satellite cells needs to be replenished so there is a supply to repair muscle in case of future injuries. In the case of muscular dystrophy, the chronic cycles of muscle regeneration and degeneration that involve satellite-cell activation exhaust the muscle stem-cell pool to the point of no return.

Our study found that by introducing an inhibitor of the STAT3 protein in repeated cycles, we could alternately replenish the pool of satellite cells and promote their differentiation into muscle fibers, said Alessandra Sacco, Ph.D., assistant professor in the Development, Aging, and Regeneration Program at Sanford-Burnham. Our results are important because the process works in mice and in human muscle cells.

Our next step is to see how long we can extend the cycling pattern, and test some of the STAT3 inhibitors currently in clinical trials for other indications such as cancer, as this could accelerate testing in humans, added Sacco.

These findings are very encouraging. Currently, there is no cure to stop or reverse any form of muscle-wasting disordersonly medication and therapy that can slow the process, said Vittorio Sartorelli, M.D., chief of the Laboratory of Muscle Stem Cells and Gene Regulation and deputy scientific director at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). A treatment approach consisting of cyclic bursts of STAT3 inhibitors could potentially restore muscle mass and function in patients, and this would be a very significant breakthrough.

Revealing the mechanism of STAT3 STAT3 (signal transducer and activator of transcription 3) is a protein that activates the transcription of genes in response to IL-6, a signaling protein released by cells in response to injury and inflammation. Prior to the study, scientists knew that STAT3 played a complex role in skeletal muscle, promoting tissue repair in some instances and hindering it in others. But the precise mechanism of how STAT3 worked was a mystery.

The research team first used normally aged mice and mice models of a form of muscular dystrophy that resembles the human disease to see what would happen if they were given a drug to inhibit STAT3. They found that the inhibitor initially promoted satellite-cell replication, followed by differentiation of the satellite cells into muscle fibers. When they injected the STAT3 inhibitor every seven days for 28 days, they found an overall improvement in skeletal-muscle repair, and an increase in the size of muscle fibers.

We were pleased to find that we achieved similar results when we performed the experiments in human muscle cells, said Sacco. We have discovered that by timing the inhibition of STAT3like an on/off light switchwe can transiently expand the satellite-cell population followed by their differentiation into mature muscle cells.

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Researchers Discover a Key to Making New Muscles

Durham, NC (PRWEB) September 05, 2014

A study published in STEM CELLS on August 30, 2014, details a new, simple, and highly efficient way to convert cells taken from an adults skin into stem cells that have the potential to differentiate into white blood cells.

Stem cells are the keystone of regenerative medicine due to their ability to be coaxed into becoming nearly any cell in the body. Induced pluripotent stem cells (iPSCs) are of particular interest because they can be generated directly from adult cells and thus many of the controversies associated with embryonic stem cells are avoided.

However, a major problem with iPSCs is their propensity to differentiate into immature cells. This is particularly true of hematopoietic (blood) cells, and the ability to generate long-term, re-populating hematopoietic stem cells has long eluded researchers.

In terms of potential clinical applications, the hematopoietic system represents one of the most suitable tissues for stem cell-based therapies as it can be relatively easily reconstituted upon bone marrow or umbilical cord blood cell transplantation. However, and even though much effort has focused on the derivation of hematopoietic cells from iPSCs, their grafting and differentiation potential remains limited, said Juan Carlos Izpisua Belmonte, Ph.D., of the Salk Institute for Biological Studies, La Jolla, Calif.

He and his colleagues at the Salk Institute, the Center of Regenerative Medicine in Barcelona, and the Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, decided to tackle this problem using a gene called Sox2 and a gene-regulating molecule called miRNA 125b. The Sox2 gene was used as a primer to coax human fibroblasts (the most common cells of connective tissue in animals) into differentiating into CD34+ cells, which are primitive blood- and bone marrow-derived progenitor cells. The miRNA 125b was then added to facilitate the differentiation of these CD34+ stem cells into more mature, hematopoietic-like stem cells.

To our knowledge this is the first time human skin cells have been converted into white blood-like cells with reconstitution and migratory potential, able to further mature in vivo and, more importantly, to graft into distant hematopoietic sites Dr. Belmonte said. Our results indicate this strategy could help circumvent obstacles to reprogramming human cells into blood cells that have clinical potential.

Jan Nolta,Ph.D., Editor-in-Chief of STEM CELLS, said, we are proud to feature this interesting work that shows that miRNA 125b facilitates the differentiation of fibroblast-derived progenitors into more mature, hematopoietic-like stem cells. This is exciting for future research into the blood-forming system. ###

The full article, Conversion of Human Fibroblasts into Monocyte-Like Progenitor Cells, can be accessed at http://onlinelibrary.wiley.com/doi/10.1002/stem.1800/abstract.

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New Study Shows Simple Conversion of Skin Cells Into White Blood-Like Cells

PUBLIC RELEASE DATE:

4-Sep-2014

Contact: Laia Cendrs laia.cendros@crg.eu 34-933-160-237 Center for Genomic Regulation

This news release is available in Spanish.

The protein Nanog, a transcription factor, is key to maintaining stem cells in a pluripotent state. Researchers from the Centre for Genomic Regulation have been investigating the role of this protein, and have just published an article in the prestigious journal Cell Reports where they reveal the mechanism whereby Nanog acts. The scientists have discovered that Nanog involves other agents and they have been able to detail their dynamics. In particular, by studying another protein that is also involved in cell reprogramming (beta-catenin) they have been able to improve the knowledge of Nanog's functioning.

Cell renewal is a natural process that takes place constantly in our body. For this to happen, we have stem cells that are responsible for generating new cells to replenish and renew those that die. Stem cells give rise to undifferentiated pluripotent cells which have the ability to become any cell type. These pluripotent cells follow a differentiation path towards specialisation, which can produce any cell type from neurones to skin.

The scientists want to understand the mechanisms that allow stem cells to either differentiate or remain pluripotent. There are also many studies that seek to reverse this process, to enable already differentiated cells to be reprogrammed and become pluripotent. Knowing all the players in these processes is of vital importance for understanding how stem cells work and allowing progress in regenerative medicine.

"We knew that Nanog was somehow involved in keeping stem cells pluripotent; now we know which mechanism it uses and we understand better how it works", explains Luca Marucci, one of the authors of the work from the cell reprogramming and regeneration laboratory at the CRG, led by researcher Pia Cosma. "Studying this process has allowed us to discover not only Nanog's key role in reprogramming, but also the dynamics of another protein, known as beta-catenin. We now know that beta-catenin, just like Nanog, continuously fluctuates in the cell and does not only appear when reprogramming is activated", adds Elisa Pedone, co-author of the work from the same laboratory.

In order to understand and define parameters for the activity of both proteins, the researchers have developed a mathematical model that could explain this dynamic. The model could be useful for understanding the behaviour of these proteins in the cell both over time and in different situations.

We are talking about a basic discovery on the functioning and dynamics of stem cell reprogramming. An ever-more studied process that holds great hope for the medicine of the future. The laboratory at the Centre for Genomic Regulation led by the ICREA research professor, Pia Cosma, is making a definitive contribution to this knowledge. Her group looks at basic mechanisms that orchestrate cell differentiation and reprogramming, right up to concrete reprogramming methods for repairing damage in certain tissues.

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New protagonist in cell reprogramming discovered