3 hours ago New genetic barcoding technology allows scientists to identify differences in origin between individual blood cells. Credit: Camargo Lab

A 7-year-project to develop a barcoding and tracking system for tissue stem cells has revealed previously unrecognized features of normal blood production: New data from Harvard Stem Cell Institute scientists at Boston Children's Hospital suggests, surprisingly, that the billions of blood cells that we produce each day are made not by blood stem cells, but rather their less pluripotent descendants, called progenitor cells. The researchers hypothesize that blood comes from stable populations of different long-lived progenitor cells that are responsible for giving rise to specific blood cell types, while blood stem cells likely act as essential reserves.

The work, supported by a National Institutes of Health Director's New Innovator Award and published in Nature, suggests that progenitor cells could potentially be just as valuable as blood stem cells for blood regeneration therapies.

This new research challenges what textbooks have long read: That blood stem cells maintain the day-to-day renewal of blood, a conclusion drawn from their importance in re-establishing blood cell populations after bone marrow transplantsa fact that still remains true. But because of a lack of tools to study how blood forms in a normal context, nobody had been able to track the origin of blood cells without doing a transplant.

Boston Children's Hospital scientist Fernando Camargo, PhD, and his postdoctoral fellow Jianlong Sun, PhD, addressed this problem with a tool that generates a unique barcode in the DNA of all blood stem cells and their progenitor cells in a mouse. When a tagged cell divides, all of its descendant cells possess the same barcode. This biological inventory system makes it possible to determine the number of stem cells/progenitors being used to make blood and how long they live, as well as answer fundamental questions about where individual blood cells come from.

"There's never been such a robust experimental method that could allow people to look at lineage relationships between mature cell types in the body without doing transplantation," Sun said. "One of the major directions we can now go is to revisit the entire blood cell hierarchy and see how the current knowledge holds true when we use this internal labeling system."

"People have tried using viruses to tag blood cells in the past, but the cells needed to be taken out of the body, infected, and re-transplanted, which raised a number of issues," said Camargo, who is a member of Children's Stem Cell Program and an associate professor in Harvard University's Department of Stem Cell and Regenerative Biology. "I wanted to figure out a way to label blood cells inside of the body, and the best idea I had was to use mobile genetic elements called transposons."

A transposon is a piece of genetic code that can jump to a random point in DNA when exposed to an enzyme called transposase. Camargo's approach works using transgenic mice that possess a single fish-derived transposon in all of their blood cells. When one of these mice is exposed to transposase, each of its blood cells' transposons changes location. The location in the DNA where a transposon moves acts as an individual cell's barcode, so that if the mouse's blood is taken a few months later, any cells with the same transposon location can be linked back to its parent cell.

The transposon barcode system took Camargo and Sun seven years to develop, and was one of Camargo's first projects when he opened his own lab at the Whitehead Institute for Biomedical Research directly out of grad school. Sun joined the project after three years of setbacks, and accomplished an experimental tour de force to reach the conclusions in the Nature paper, which includes data on how many stem cells or progenitor cells contribute to the formation of immune cells in mouse blood.

With the original question of how blood arises in a non-transplant context answered, the researchers are now planning to explore many more applications for their barcode tool.

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Barcoding tool for stem cells: New technology that tracks the origin of blood cells challenges scientific dogma

HOUSTON -

Stem cells, the body's so called "master cells," are used to treat heart disease and cancer and to grow tissue. But plants also have stem cells and they're some of the hottest ingredients in anti-aging products.

Andrea Vizcaino, 49, is trying out a new phyto-facial that comes in the form of a freeze dried serum in a vial. One of the main ingredients is stem cells from the argon tree in Morocco. She described the procedure.

"It feels warm, especially around my chin and it feels good," said Vizcaino. "Very hydrating; the skin feels moist."

Apple, echinacea and grape stem cells are already used in many skin care products, but some scientists think the argon tree cells will penetrate even deeper.

"The plant stem cells stimulate our stem cells to regenerate the skin," said skin care specialist Candy Bonura.

Allenby agrees the new products can be hydrating, but said the jury is still out about the real effectiveness of plant stem cells.

"Stem cells are kind of the buzz word right now, but we have to remember that stem cells are different in plants and different in people," Allenby said.

Bonura acknowledged these new products won't take years off your face, but many clients do see a difference.

"I see a brightening, I see a hydration, I also see the skin is more supple looking and more youthful with a glow to it," Bonura said.

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Plant stem cells may help skin look younger, healthier

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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

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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

11 hours 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

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

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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.

###

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

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

Aired 9/12/14 on KPBS News.

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

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

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

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

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(Phys.org) For 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.

The researchers are now conducting toxicology studies and cell transplantation proof-of-concept studies in advance of potential preclinical and clinical studies.

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Simple method turns human skin cells into immune-fighting white blood 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

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