Dec. 18, 2013 Regenerative medicine may offer ways to banish baldness that don't involve toupees. The lab of USC scientist Krzysztof Kobielak, MD, PhD has published a trio of papers in the journals Stem Cells and The Proceedings of the National Academy of Sciences (PNAS) that describe some of the factors that determine when hair grows, when it stops growing and when it falls out.

Authored by Kobielak, postdoctoral fellow Eve Kandyba, PhD, and their colleagues, the three publications focus on stem cells located in hair follicles (hfSCs), which can regenerate hair follicles as well as skin. These hfSCs are governed by the signaling pathways BMP and Wnt -- which are groups of molecules that work together to control cell functions, including the cycles of hair growth.

The most recent paper, published in the journal Stem Cells in November 2013, focuses on how the gene Wnt7b activates hair growth. Without Wnt7b, hair is much shorter.

The Kobielak lab first proposed Wnt7b's role in a January 2013 PNAS publication. The paper identified a complex network of genes -- including the Wnt and BMP signaling pathways -- controlling the cycles of hair growth. Reduced BMP signaling and increased Wnt signaling activate hair growth. The inverse -- increased BMP signaling and decreased Wnt signaling -- keeps the hfSCs in a resting state.

Both papers earned the recommendation of the Faculty of 1000, which rates top articles by leading experts in biology and medicine.

A third paper published in Stem Cells in September 2013 further clarified the workings of the BMP signaling pathway by examining the function of two key proteins, called Smad1 and Smad5. These proteins transmit the signals necessary for regulating hair stem cells during new growth.

"Collectively, these new discoveries advance basic science and, more importantly, might translate into novel therapeutics for various human diseases," said Kobielak. "Since BMP signaling has a key regulatory role in maintaining the stability of different types of adult stem cell populations, the implication for future therapies might be potentially much broader than baldness -- and could include skin regeneration for burn patients and skin cancer."

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Stem cells offer clues to reversing receding hairlines

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Highlights Investigators have discovered a cocktail of chemicals which, when added to stem cells in a precise order, turns on genes found in kidney cells in the same order that they turn on during embryonic kidney development. The kidney cells continued to behave like kidney cells when transplanted into adult or embryonic mouse kidneys.

Newswise Washington, DC (December 19, 2013) Researchers have successfully coaxed stem cells to become kidney tubular cells, a significant advance toward one day using regenerative medicine, rather than dialysis and transplantation, to treat kidney failure. The findings are published in the Journal of the American Society of Nephrology (JASN).

Chronic kidney disease is a major global public health problem, and when patients progress to kidney failure, their treatment options are limited to dialysis and kidney transplantation. Regenerative medicinewhich involves rebuilding or repairing tissues and organsmay offer a promising alternative.

Albert Lam, MD, Benjamin Freedman, PhD, Ryuji Morizane, MD, PhD (Brigham and Womens Hospital), and their colleagues have been working for the past five years to develop strategies to coax human pluripotent stem cellsparticularly human embryonic stem (ES) cells and human induced pluripotent stem (iPS) cellinto kidney cells for the purposes of kidney regeneration.

Our goal was to develop a simple, efficient, and reproducible method of differentiating human pluripotent stem cells into cells of the intermediate mesoderm, the earliest tissue in the developing embryo that is fated to give rise to the kidneys, said Dr. Lam. He noted that these cells would be the starting blocks for deriving more specific kidney cells.

The researchers discovered a cocktail of chemicals which, when added to stem cells in a precise order, causes them to turn off genes found in ES cells and turn on genes found in kidney cells, in the same order that they turn on during embryonic kidney development. The investigators were able to differentiate both human ES cells and human iPS cells into cells expressing PAX2 and LHX1, two key markers of the intermediate mesoderm. The iPS cells were derived by transforming fibroblasts obtained from adult skin biopsies to pluripotent cells, making the techniques applicable to personalized approaches where the starting cells can be derived from skin cells of a patient. The differentiated cells expressed multiple genes expressed in intermediate mesoderm and could spontaneously give rise to tubular structures that expressed markers of mature kidney tubules. The researchers could then differentiate them further into cells expressing SIX2, SALL1, and WT1, important markers of the metanephric cap mesenchyme, a critical stage of kidney differentiation. In kidney development, the metanephric cap mesenchyme contains a population of progenitor cells that give rise to nearly all of the epithelial cells of the kidney.

The cells also continued to behave like kidney cells when transplanted into adult or embryonic mouse kidneys, giving hope that investigators might one day be able to create kidney tissues that could function in a patient and would be 100% immunocompatible.

We believe that the successful derivation of kidney progenitor cells or functional kidney cells from human pluripotent stem cells will have an enormous impact on a variety of clinical and translational applications, including kidney tissue bioengineering, renal assist devices to treat acute and chronic kidney injury, drug toxicity screening, screening for novel therapeutics, and human kidney disease modeling, said Dr. Lam.

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Researchers Generate Kidney Tubular Cells From Stem Cells

Abba Zubair, medical and scientific director of the Cell Therapy Laboratory at the Mayo Clinic in Jacksonville, wants to test the feasibility of growing stem cells in outer space, cells that could be used to generate new tissue and even new organs in human beings.

There are reasons to believe that stem cells, which are hard to grow in the great quantity they are needed on Earth, will grow much more rapidly in the microgravity environment in space, Zubair thinks. Now the Center for the Advancement in Science in Space has given Zubair a $300,000 grant to test that by placing stem cells in a specialized cell bioreactor in the International Space Station.

It now takes a month to generate enough cells for a few patients, Zubair said. A clinical laboratory in space could provide the answer we all have been seeking for regenerative medicine. ... If you have a ready supply of these cells, you can treat almost any condition and can theoretically regenerate entire organs using a scaffold. Additionally, they dont need to come from individual patients. Anyone can use them without rejection.

The stem cells he plans to grow in space will be stem cells that can induce regeneration of neurons and blood vessels in patients who have suffered hemorrhagic strokes caused by blood clots.

I have a special personal interest in stroke, Zubair said. Thats what killed my mom years ago. I really would like to conquer and treat stroke.

The first step in growing stem cells in space is happening at the University of Colorado where engineers are building the cell bioreactor Zubair will use on the space station. Within a year, Zubair hopes to transport the bioreactor and stem cells to the space station, perhaps aboard a flight by SpaceX, a company expected to begin commercial flights to the space station soon.

Once the bioreactor and stem cells are aboard the space station, it will take about a month to grow them, Zubair said. The results will then be analyzed by the astronauts on the space station and by researches back in Zubairs Jacksonville laboratories.

We will be trying to determine if our notion that stem cells grow faster in microgravity is true, Zubair said. We also want to know how feasible it is to produce clinical grade cells in space that can be used in humans.

Hes optimistic his study will show that growing stem cells in space is a viable way to create stem cells in quantity.

Were quite excited, he said. I really think the future is full of promise. We just have to take the opportunity to make that a reality.

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Mayo cell therapy researcher plans to grow stem cells in space, where he thinks they will grow faster than on Earth

Stem Cell Therapy - Facet Syndrome Patients Relieve Back and Neck Pain Dr Robert Wagner - NSPC
How to know if the cause of your back or neck pain is Facet Syndrome. Discover how biologic regenerative treatments are able to pick up where traditional tre...

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Poway, CA (PRWEB) December 19, 2013

Amazing Grace Hamiltons banked stem cells from Vet-Stem, Inc. have recently helped her avoid hip surgery for the second time. Gracie is now nearly 12 years old and her owners noticed her activities had dramatically slowed in the last year. They turned to banked stem cells that Gracie had stored with Vet-Stem, Inc. in Poway, California to help with the discomfort and pain of arthritis that was slowing her down.

When Gracies owners brought her to Garden State Veterinary Specialists in Tinton Falls, New Jersey in October of this year the x-rays showed a severely deteriorated right hip. Dr. Thomas Scavelli and Dr. Michael Hoelzler were very concerned and recommended hip replacement. Gracies owners wanted to try stem cell therapy first, since it had given them such positive results five years before.

We needed to give the stem cells a try before going to the more invasive surgical approach, Mrs. Hamilton said. At the time of the procedure Dr. Hoelzler told me that Gracies hips were the worst he had seen, but in just a couple of days after the stem cell therapy we began to see a difference. Just shy of two weeks after the procedure I took her back to Dr. Hoelzler and he was very impressed. She was walking comfortably.

At three years Gracie had been diagnosed with hip dysplasia. By six years of age she had slowed to the point of great concern as her owners described it. The pain caused by arthritis from the hip dysplasia was beginning to interfere with her life.

Gracie was no longer running and jumping, and certain activities had become difficult (like climbing onto my husbands sailboat). She also had a noticeable limp, Mrs. Hamilton remembered the signs of pain and discomfort that prompted Gracies first stem cell therapy five years before.

Gracie was brought to Dr. Scavelli in 2008 with painful symptoms, and stem cell therapy for pets was the latest, cutting edge treatment. Gracies owners understood that without stem cell therapy Gracie would have faced hip surgery at the time.

We are grateful for stem cell therapy which has restored Gracies ability to enjoy her morning walks again, Mrs. Hamilton shared, She enjoys wrestling with us and playing with her toys. She looks forward to visiting her friends, and prances around like a puppy. Gracie is a happy dog and we are happy owners because she does not appear to be in pain anymore!

About Vet-Stem, Inc.

Vet-Stem, Inc. was formed in 2002 to bring regenerative medicine to the veterinary profession. The privately held company is working to develop therapies in veterinary medicine that apply regenerative technologies while utilizing the natural healing properties inherent in all animals. As the first company in the United States to provide an adipose-derived stem cell service to veterinarians for their patients, Vet-Stem, Inc. pioneered the use of regenerative stem cells in veterinary medicine. The company holds exclusive licenses to over 50 patents including world-wide veterinary rights for use of adipose derived stem cells. In the last decade over 10,000 animals have been treated using Vet-Stem, Inc.s services, and Vet-Stem is actively investigating stem cell therapy for immune-mediated and inflammatory disease, as well as organ disease and failure. For more on Vet-Stem, Inc. and Veterinary Regenerative Medicine visit http://www.vet-stem.com or call 858-748-2004.

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Stem Cell Therapy by Vet-Stem, a Surprising Alternative to Hip Surgery for a New Jersey Chocolate Labrador Retriever

In a typical stem cell transplant for cancer very high doses of chemo are used, often along with radiation therapy, to try to destroy all the cancer cells. This treatment also kills the stem cells in the bone marrow. Soon after treatment, stem cells are given to replace those that were destroyed. These stem cells are given into a vein, much like a blood transfusion. Over time they settle in the bone marrow and begin to grow and make healthy blood cells. This process is called engraftment.

There are 3 basic types of transplants. They are named based on who gives the stem cells.

These stem cells come from you alone. In this type of transplant, your stem cells are taken before you get cancer treatment that destroys them. Your stem cells are removed, or harvested, from either your bone marrow or your blood and then frozen. To find out more about that process, please see the section Whats it like to donate stem cells? After you get high doses of chemo and/or radiation the stem cells are thawed and given back to you.

One advantage of autologous stem cell transplant is that you are getting your own cells back. When you donate your own stem cells you dont have to worry about the graft attacking your body (graft-versus-host disease) or about getting a new infection from another person. But there can still be graft failure, and autologous transplants cant produce the graft-versus-cancer" effect.

This kind of transplant is mainly used to treat certain leukemias, lymphomas, and multiple myeloma. Its sometimes used for other cancers, like testicular cancer and neuroblastoma, and certain cancers in children. Doctors are looking at how autologous transplants might be used to treat other diseases, too, like systemic sclerosis, multiple sclerosis, Crohn disease, and systemic lupus erythematosis.

A possible disadvantage of an autologous transplant is that cancer cells may be picked up along with the stem cells and then put back into your body later. Another disadvantage is that your immune system is still the same as before when your stem cells engraft. The cancer cells were able to grow despite your immune cells before, and may be able to do so again.

To prevent this, doctors may give you anti-cancer drugs or treat your stem cells in other ways to reduce the number of cancer cells that may be present. Some centers treat the stem cells to try to remove any cancer cells before they are given back to the patient. This is sometimes called purging. It isnt clear that this really helps, as it has not yet been proven to reduce the risk of cancer coming back (recurrence).

A possible downside of purging is that some normal stem cells can be lost during this process, causing the patient to take longer to begin making normal blood cells, and have unsafe levels of white blood cells or platelets for a longer time. This could increase the risk of infections or bleeding problems.

One popular method now is to give the stem cells without treating them. Then, after transplant, the patient gets a medicine to get rid of cancer cells that may be in the body. This is called in vivo purging. Rituximab (Rituxan), a monoclonal antibody drug, may be used for this in certain lymphomas and leukemias, and other drugs are being tested. The need to remove cancer cells from transplants or transplant patients and the best way to do it is being researched.

Doing 2 autologous transplants in a row is known as a tandem transplant or a double autologous transplant. In this type of transplant, the patient gets 2 courses of high-dose chemo, each followed by a transplant of their own stem cells. All of the stem cells needed are collected before the first high-dose chemo treatment, and half of them are used for each transplant. Most often both courses of chemo are given within 6 months, with the second one given after the patient recovers from the first one.

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Types of stem cell transplants for treating cancer

Durham, NC (PRWEB) December 18, 2013

A new study released today in STEM CELLS Translational Medicine demonstrates that the therapeutic value of stem cells collected from fat declines when the cells come from older patients.

This could restrict the effectiveness of autologous cell therapy using fat, or adipose-derived mesenchymal stromal cells (ADSCs), and require that we test cell material before use and develop ways to pretreat ADSCs from aged patients to enhance their therapeutic potential, said Anastasia Efimenko, M.D., Ph.D. She and Nina Dzhoyashvili, M.D., were first authors of the study led by Yelena Parfyonova, M.D., D.Sc., at Lomonosov Moscow State University, Moscow.

Cardiovascular disease remains the most common cause of death in most countries. Mesenchymal stromal cells (MSCs), stem cells collected from either bone marrow or adipose tissue, are considered one of the most promising therapeutic agents for regenerating damaged tissue because of their proliferation potential and ability to be coaxed into different cell types. Importantly, they also have the ability to stimulate the growth of new blood vessels, a process known as angiogenesis.

Adipose tissue in particular is considered an ideal source for MSCs because it is largely dispensable and the stem cells are easily accessible in large amounts using a minimally invasive procedure. ADSCs have been used in several clinical trials looking at cell therapy for heart conditions, but most of the studies employed cells taken from relatively healthy young donors rather than sick, older ones the typical patient when it comes to heart disease.

We knew that aging and disease itself may negatively affect MSC activities, Dr. Dzhoyashvili said. So the aim of our study was to investigate how patient age affects the properties of ADSCs, with special emphasis on their ability to stimulate angiogenesis.

The team analyzed age-associated changes in ADSCs collected from patients of different age groups, including some with coronary artery disease and some without. The results showed that ADSCs from the older patients in both groups expressed various age markers, including shorter telomeres, and, thus, confirmed that ADSCs did age. Telomeres, the regions of repetitive DNA at the end of a chromosome, protect it from deterioration.

We showed that ADSCs from older patients both with and without coronary artery disease produced significantly less amounts of angiogenesis-stimulating factors compared with the younger patients in the study and their angiogenic capabilities lessened, Dr. Efimenko concluded. The results provide new insight into molecular mechanisms underlying the age-related decline of stem cells therapeutic potential.

These findings are significant because the successful development of cell therapies depends on a thorough understanding of how age may affect the regenerative potential of autologous cells, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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Study Shows Therapeutic Potential of Fat-derived Stem Cells Declines As Donor’s Age Rises

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18-Dec-2013

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (Dec. 18, 2013) Multiple sclerosis (MS), an inflammatory autoimmune disease affecting more than one million people worldwide, is caused by an immune reaction to myelin proteins, the proteins that help form the myelin insulating substance around nerves. Demyelination and MS are a consequence of this immune reaction. Bone marrow mesenchymal stem cells (MSCs) have been considered as an important source for cell therapy for autoimmune diseases such as MS because of their immunosuppressive properties.

Now, a research team in Brazil has compared MSCs isolated from MS patients and from healthy donors to determine if the MSCs from MS patients are normal or defective. The study will be published in a future issue of Cell Transplantation but is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct1131.

"The ability of MSCs to modulate the immune response suggests a possible role of these cells in tolerance induction in patients with autoimmune diseases, and also supports the rationale for MSC application in the treatment of MS," said study corresponding author Dr. Gislane Lelis Vilela de Oliveira of the Center for Cell-Based Research at the University of Sao Paulo. "We found that MS patient-derived MSCs present higher senescence, or biological aging, and decreased expression of important immune system markers as well as a different transcriptional profile when compared to their healthy counterparts."

The researchers suggested that further clinical studies should be conducted using transplanted allogenic (other-donated) MSCs derived from healthy donors to determine if the MSCs have a therapeutic effect over transplanted autologous (self-donated) MSCs from patients.

"Several reports have shown that bone marrow-derived MSCs are able to modulate innate and adaptive immunity cell responses and induce tolerance, thus supporting the rationale for their application in treating autoimmune diseases, " said the researchers.

They also noted that studies have shown that transplanted MSCs migrate to demyelinated areas as well as induce generation and expansion of regulatory T cells, important in immunity.

"We found that the transcriptional profile of patient MSCs after transplantation was closer to that of their pre-transplant MSC samples than those from their healthy counterparts, suggesting that treatment with patient self-donated MSCs does not reverse the alterations we observed in MSCs from MS patients," they concluded.

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18-Dec-2013

Contact: Kevin Punsky punsky.kevin@mayo.edu 904-953-2299 Mayo Clinic

JACKSONVILLE, Fla. -- Abba Zubair, M.D., Ph.D, believes that cells grown in the International Space Station (ISS) could help patients recover from a stroke, and that it may even be possible to generate human tissues and organs in space. He just needs a chance to demonstrate the possibility.

He now has it. The Center for the Advancement of Science in Space (CASIS), a nonprofit organization that promotes research aboard the ISS, has awarded Dr. Zubair a $300,000 grant to send human stem cells into space to see if they grow more rapidly than stem cells grown on Earth.

Dr. Zubair, medical and scientific director of the Cell Therapy Laboratory at Mayo Clinic in Florida, says the experiment will be the first one Mayo Clinic has conducted in space and the first to use these human stem cells, which are found in bone marrow.

"On Earth, we face many challenges in trying to grow enough stem cells to treat patients," he says. "It now takes a month to generate enough cells for a few patients. A clinical-grade laboratory in space could provide the answer we all have been seeking for regenerative medicine."

He specifically wants to expand the population of stem cells that will induce regeneration of neurons and blood vessels in patients who have suffered a hemorrhagic stroke, the kind of stroke which is caused by blood clot. Dr. Zubair already grows such cells in his Mayo Clinic laboratory using a large tissue culture and several incubators -- but only at a snail's pace.

Experiments on Earth using microgravity have shown that stem cells -- the master cells that produce all organ and tissue cell types -- will grow faster, compared to conventionally grown cells.

"If you have a ready supply of these cells, you can treat almost any condition, and can theoretically regenerate entire organs using a scaffold," Dr. Zubair says. "Additionally, they don't need to come from individual patients -- anyone can use them without rejection."

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Mayo Clinic researcher to grow human cells in space to test treatment for stroke

Gypenosides pre-treatment protects the brain against cerebral ischemia and increases neural stem cells/progenitors in the subventricular zone.

Gypenosides pre-treatment protects the brain against cerebral ischemia and increases neural stem cells/progenitors in the subventricular zone.

Int J Dev Neurosci. 2013 Dec 12;

Authors: Wang XJ, Sun T, Kong L, Shang ZH, Yang KQ, Zhang QY, Jing FM, Dong L, Xu XF, Liu JX, Xin H, Chen ZY

Abstract Gypenosides (GPs) have been reported to have neuroprotective effects in addition to other bioactivities. The protective activity of GPs during stroke and their effects on neural stem cells (NSCs) in the ischemic brain have not been fully elucidated. Here, we test the effects of GPs during stroke and on the NSCs within the subventricular zone (SVZ) of middle cerebral artery occlusion (MCAO) rats. Our results show that pre-treatment with GPs can reduce infarct volume and improve motor function following MCAO. Pre-treatment with GPs significantly increased the number of BrdU-positive cells in the ipsilateral and contralateral SVZ of MCAO rats. The proliferating cells in both sides of the SVZ were glial fibrillary acidic protein (GFAP)/nestin-positive type B cells and Doublecortin (DCX)/nestin-positive type A cells. Our data indicate that GPs have neuroprotective effects during stroke which might be mediated through the enhancement of neurogenesis within the SVZ. These findings provide new evidence for a potential therapy involving GPs for the treatment of stroke.

PMID: 24334222 [PubMed - as supplied by publisher]

Cell based therapies for ischemic stroke: from basic science to bedside.

Prog Neurobiol. 2013 Dec 12;

Authors: Liu X, Ye R, Yan T, Yu SP, Wei L, Xu G, Fan X, Jiang Y, Stetler RA, Chen J

Abstract Cell therapy is emerging as a viable therapy to restore neurological function after stroke. Many types of stem/progenitor cells from different sources have been explored for their feasibility and efficacy for the treatment of stroke. Transplanted cells not only have the potential to replace the lost circuitry, but also produce growth and trophic factors, or stimulate the release of such factors from host brain cells, thereby enhancing endogenous brain repair processes. Although stem/progenitor cells have shown a promising role in ischemic stroke in experimental studies as well as initial clinical pilot studies, cellular therapy is still at an early stage in humans. Many critical issues need to be addressed including the therapeutic time window, cell type selection, delivery route, and in vivo monitoring of their migration pattern. This review attempts to provide a comprehensive synopsis of preclinical evidence and clinical experience of various donor cell types, their restorative mechanisms, delivery routes, imaging strategies, future prospects and challenges for translating cell therapies as a neurorestorative regimen in clinical applications.

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Stroke and Stem Cell Therapy

Shutdowns, lethal viruses, typhoons and meteorites much of this years science news seemed to come straight from the set of a Hollywood disaster movie. But there were plenty of feel-good moments, too. Space exploration hit a new high, cash poured in to investigate that most cryptic of human organs, the brain, and huge leaps were made in stem-cell therapies and the treatment of HIV. Here, captured in soundbites, statistics and summaries, is everything you need to know about the science that mattered in 2013.

LUX: Carlos H. Faham

The Large Underground Xenon dark-matter experiment, deep in a mine in South Dakota.

One of the years most important cosmological results was an experimental no-show. The Large Underground Xenon (LUX, pictured) experiment at Sanford Underground Research Facility in Lead, South Dakota 370 kilograms of liquid xenon almost 1.5kilometres down in a gold mine did not see any particles of elusive dark matter flying through Earth. But it put the tightest constraints yet on the mass of dark-matter particles, and their propensity to interact with visible matter. Theoretical physicist Matthew Strassler at Rutgers University in Piscataway, New Jersey, says a consensus is forming that hints of dark matter seen by earlier experiments in the past three years were probably just statistical fluctuations.

PlancK: ESA/Planck Collaboration

Whatever dark matter is, it makes up around 84% of the Universes total matter, according to observations, released in March, of the Universes cosmic microwave background (CMB) by the European Space Agencys Planck satellite. Plancks image (pictured) also strongly supports the hypothesis of inflation, in which the Universe is thought to have expanded rapidly after the Big Bang. A better probe of inflation might be provided through its predicted influence on how the polarization of CMB photons varies across the sky (B-mode polarization). That subtle signal has not been measured yet, but astronomers hopes were raised by news of the first sighting of a related polarization signal, by the South Pole Telescope, in July. And another Antarctic telescope the underground IceCube observatory confirmed this year that the high-energy neutrinos it has detected come from far away in the cosmos, hinting at a new world of neutrino astronomy.

Jae C. Hong/AP

US workers came out in force against the shutdown.

The slow decline of US federal support for research and development spending is already down 16.3% since 2010 reached a new nadir in October, when political brinkmanship led the government to shut down for 16 days. Grant money stopped flowing; work halted at major telescopes, US Antarctic bases and most federal laboratories; and key databases maintained by the government went offline. Many government researchers were declared non-essential and barred by law from visiting their offices and laboratories, or even checking their official e-mail accounts. Since the shutdowns end, grant backlogs and missed deadlines have scrambled agency workloads.

Away from the deadlock in the United States, the European Union negotiated a path to a 201420 research budget of almost 80billion (US$110billion), a 27% rise in real terms over the previous 200713 period. And funding in South Korea, China, Germany and Japan continued to increase (the United Kingdom and France saw little change). But Japans largesse came with the clear understanding that its science investment would bring fast commercial pay-offs. Along similar lines, US Republican politicians are calling for the National Science Foundation to justify every grant it awards as being in the national interest.

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365 days: 2013 in review

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Newswise Researchers at UCLAs Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered a mechanism in adult stem cells by which the cells suppress their ability to initiate cancer during their dormant phase, an understanding that could be exploited for better cancer prevention strategies. The study was led by Andrew White, post-doctoral fellow, and William Lowry, associate professor of molecular, cell and developmental biology in the life sciences and the Maria Rowena Ross Term Chair in Cell Biology.

The study was published online ahead of print in Nature Cell Biology on December 15, 2013.

Hair follicle stem cells (HFSC), the tissue-specific adult stem cells that generate the hair follicles, are also the cells of origin for cutaneous squamous cell carcinoma (SCC), a common skin cancer. These HFSCs cycle between periods of activation, during which they can grow, and quiescence, when they remain dormant.

Using mouse models, White and Lowry applied known cancer-causing genes (oncogenes) to HFSCs and found that during cell quiescence, the cells could not be made to initiate SCC. Once the HFSC were in their active period, they began growing cancer.

We found that this tumor suppression via adult stem cell quiescence was mediated by Pten, a gene important in regulating the cells response to signaling pathways, White said, therefore, stem cell quiescence is a novel form of tumor suppression in hair follicle stem cells, and Pten must be present for the suppression to work.

Understanding cancer suppression through quiescence could better inform preventative strategies in patients susceptible to SCC, such as organ transplant patients, or those taking the drug vemurafenib for melanoma, another type of skin cancer. This study also may reveal parallels between SCC and other cancers in which stem cells have a quiescent phase. This research was supported by the California Institute of Regenerative Medicine (CIRM), University of California Cancer Research Coordinating Committee (CRCC) and National institutes of Health (NIH).

The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLAs Jonsson Comprehensive Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu.

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Adult Stem Cells Found to Suppress Cancer While Dormant

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17-Dec-2013

Contact: Press Office biologypress@plos.org Public Library of Science

A systematic survey of the scientific literature shows that stem cell therapy can have a statistically significant impact on animal models of spinal cord injury, and points the way for future studies.

Spinal cord injuries are mostly caused by trauma, often incurred in road traffic or sporting incidents, often with devastating and irreversible consequences, and unfortunately having a relatively high prevalence (250,000 patients in the USA; 80% of cases are male). High-profile campaigners like the late actor Christopher Reeve, himself a victim of sports-related spinal cord injury, have placed high hopes in stem cell transplantation. But how likely is it to work?

This question is addressed in a paper published 17th December in the open access journal PLOS Biology by Ana Antonic, David Howells and colleagues from the Florey Institute and the University of Melbourne, Australia, and Malcolm MacLeod and colleagues from the University of Edinburgh, UK.

Stem cell therapy aims to use special regenerative cells (stem cells) to repopulate areas of damage that result from spinal cord injuries, with the hope of improving the ability to move ("motor outcomes") and to feel ("sensory outcomes") beyond the site of the injury. Many studies have been performed that involve animal models of spinal cord injury (mostly rats and mice), but these are limited in scale by financial, practical and ethical considerations. These limitations hamper each individual study's statistical power to detect the true effects of the stem cell implantation.

This new study gets round this problem by conducting a "meta-analysis" a sophisticated and systematic cumulative statistical reappraisal of many previous laboratory experiments. In this case the authors assessed 156 published studies that examined the effects of stem cell treatment for experimental spinal injury in a total of about 6000 animals.

Overall, they found that stem cell treatment results in an average improvement of about 25% over the post-injury performance in both sensory and motor outcomes, though the results can vary widely between animals. For sensory outcomes the degree of improvement tended to increase with the number of cells introduced scientists are often reassured by this sort of "dose response", as it suggests a real underlying biologically plausible effect.

The authors went on to use their analysis to explore the effects of bias (whether the experimenters knew which animals were treated and which untreated), the way that the stem cells were cultured, the way that the spinal injury was generated, and the way that outcomes were measured. In each case, important lessons were learned that should help inform and refine the design of future animal studies. The meta-analysis also revealed some surprises that should provoke further investigation there was little evidence of any beneficial sensory effects in female animals, for example, and it didn't seem to matter whether immunosuppressive drugs were administered or not.

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Will stem cell therapy help cure spinal cord injury?

PUBLIC RELEASE DATE:

16-Dec-2013

Contact: Shaun Mason smason@mednet.ucla.edu 310-206-2805 University of California - Los Angeles

Scientists from UCLA are now bringing their groundbreaking stem cell science directly to patients in two exciting new clinical trials scheduled to begin in early 2014, thanks to funding from California's stem cell agency.

The new grants to researchers at UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, which total nearly $21 million, were announced Dec. 12 at a meeting of the California Institute of Regenerative Medicine (CIRM) Citizen's Oversight Committee. They are apart of the state agency's Disease Team Therapy Development III initiative.

A team led by UCLA's Dr. Dennis Slamon and Dr. Zev Wainberg was awarded nearly $7 million for a clinical trial that will test a new drug targeting cancer stem cells, and UCLA's Dr. Donald Kohn received almost $14 million for a clinical trial that will focus on stem-cell gene therapy for sickle cell disease.

"The CIRM support demonstrates that our multidisciplinary center is at the forefront of translating basic scientific research into new drug and cellular therapies that will revolutionize medicine," said Dr. Owen Witte, director of the UCLA Broad Stem Cell Research Center.

Dennis Slamon and Zev Wainberg: Targeting solid tumor stem cells

This clinical trial builds on Slamon's previous work, partially funded by CIRM, with Wainberg and Dr. Tak Mak, director of the Campbell Family Institute at the University Health Network in Toronto, aimed at developing a drug that targets those stem cells thought to initiate solid cancer tumors.

The AmericanCanadian collaborative team will lead this first in-human Phase 1 trial testing their new therapy, which has received investigational new-drug approval from the U.S. Food and Drug Administration and Health Canada, Canada's therapeutic regulatory agency. The project has been approved to begin enrolling patients in both the U.S. and Canada.

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With new multimillion-dollar grants, UCLA scientists take stem cell research to patients

PUBLIC RELEASE DATE:

16-Dec-2013

Contact: Jennifer Schutz newsbureau@mayo.edu 507-284-5005 Mayo Clinic

ROCHESTER, Minn. -- Mayo Clinic researchers and colleagues in Belgium have developed a specialized catheter for transplanting stem cells into the beating heart. The novel device includes a curved needle and graded openings along the needle shaft, allowing for increased distribution of cells. The result is maximized retention of stem cells to repair the heart. The findings appear in the journal Circulation: Cardiovascular Interventions.

"Although biotherapies are increasingly more sophisticated, the tools for delivering regenerative therapies demonstrate a limited capacity in achieving high cell retention in the heart," says Atta Behfar, M.D., Ph.D., a Mayo Clinic cardiology specialist and lead author of the study. "Retention of cells is, of course, crucial to an effective, practical therapy."

Researchers from the Mayo Clinic Center for Regenerative Medicine in Rochester and Cardio3 Biosciences in Mont-Saint-Guibert, Belgium, collaborated to develop the device, beginning with computer modeling in Belgium. Once refined, the computer-based models were tested in North America for safety and retention efficiency.

What's the significance?

This new catheter is being used in the European CHART-1 clinical trials, now underway. This is the first Phase III trial to regenerate hearts of patients who have suffered heart attack damage. The studies are the outcome of years of basic science research at Mayo Clinic and earlier clinical studies with Cardio3 BioSciences and Cardiovascular Centre in Aalst, Belgium, conducted between 2009 and 2010.

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The development of the catheter and subsequent studies were supported by Cardio3 BioSciences; Walloon Region General Directorate for Economy, Employment & Research; Meijer Lavino Foundation for Cardiac Research Aalst (Belgium); the National Institutes of Health; Grainger Foundation; Florida Heart Research Institute; Marriott Heart Disease Research Program; and the Mayo Clinic Center for Regenerative Medicine.

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Regenerative medicine: Mayo Clinic and collaborators develop new tool for transplanting stem cells

by Jos Domen*, Amy Wagers** and Irving L. Weissman***

Blood and the system that forms it, known as the hematopoietic system, consist of many cell types with specialized functions (see Figure 2.1). Red blood cells (erythrocytes) carry oxygen to the tissues. Platelets (derived from megakaryocytes) help prevent bleeding. Granulocytes (neutrophils, basophils and eosinophils) and macrophages (collectively known as myeloid cells) fight infections from bacteria, fungi, and other parasites such as nematodes (ubiquitous small worms). Some of these cells are also involved in tissue and bone remodeling and removal of dead cells. B-lymphocytes produce antibodies, while T-lymphocytes can directly kill or isolate by inflammation cells recognized as foreign to the body, including many virus-infected cells and cancer cells. Many blood cells are short-lived and need to be replenished continuously; the average human requires approximately one hundred billion new hematopoietic cells each day. The continued production of these cells depends directly on the presence of Hematopoietic Stem Cells (HSCs), the ultimate, and only, source of all these cells.

Figure 2.1. Hematopoietic and stromal cell differentiation.

2001 Terese Winslow (assisted by Lydia Kibiuk)

The search for stem cells began in the aftermath of the bombings in Hiroshima and Nagasaki in 1945. Those who died over a prolonged period from lower doses of radiation had compromised hematopoietic systems that could not regenerate either sufficient white blood cells to protect against otherwise nonpathogenic infections or enough platelets to clot their blood. Higher doses of radiation also killed the stem cells of the intestinal tract, resulting in more rapid death. Later, it was demonstrated that mice that were given doses of whole body X-irradiation developed the same radiation syndromes; at the minimal lethal dose, the mice died from hematopoietic failure approximately two weeks after radiation exposure.1 Significantly, however, shielding a single bone or the spleen from radiation prevented this irradiation syndrome. Soon thereafter, using inbred strains of mice, scientists showed that whole-body-irradiated mice could be rescued from otherwise fatal hematopoietic failure by injection of suspensions of cells from blood-forming organs such as the bone marrow.2 In 1956, three laboratories demonstrated that the injected bone marrow cells directly regenerated the blood-forming system, rather than releasing factors that caused the recipients' cells to repair irradiation damage.35 To date, the only known treatment for hematopoietic failure following whole body irradiation is transplantation of bone marrow cells or HSCs to regenerate the blood-forming system in the host organisms.6,7

The hematopoietic system is not only destroyed by the lowest doses of lethal X-irradiation (it is the most sensitive of the affected vital organs), but also by chemotherapeutic agents that kill dividing cells. By the 1960s, physicians who sought to treat cancer that had spread (metastasized) beyond the primary cancer site attempted to take advantage of the fact that a large fraction of cancer cells are undergoing cell division at any given point in time. They began using agents (e.g., chemical and X-irradiation) that kill dividing cells to attempt to kill the cancer cells. This required the development of a quantitative assessment of damage to the cancer cells compared that inflicted on normal cells. Till and McCulloch began to assess quantitatively the radiation sensitivity of one normal cell type, the bone marrow cells used in transplantation, as it exists in the body. They found that, at sub-radioprotective doses of bone marrow cells, mice that died 1015 days after irradiation developed colonies of myeloid and erythroid cells (see Figure 2.1 for an example) in their spleens. These colonies correlated directly in number with the number of bone marrow cells originally injected (approximately 1 colony per 7,000 bone marrow cells injected).8 To test whether these colonies of blood cells derived from single precursor cells, they pre-irradiated the bone marrow donors with low doses of irradiation that would induce unique chromosome breaks in most hematopoietic cells but allow some cells to survive. Surviving cells displayed radiation-induced and repaired chromosomal breaks that marked each clonogenic (colony-initiating) hematopoietic cell.9 The researchers discovered that all dividing cells within a single spleen colony, which contained different types of blood cells, contained the same unique chromosomal marker. Each colony displayed its own unique chromosomal marker, seen in its dividing cells.9 Furthermore, when cells from a single spleen colony were re-injected into a second set of lethally-irradiated mice, donor-derived spleen colonies that contained the same unique chromosomal marker were often observed, indicating that these colonies had been regenerated from the same, single cell that had generated the first colony. Rarely, these colonies contained sufficient numbers of regenerative cells both to radioprotect secondary recipients (e.g., to prevent their deaths from radiation-induced blood cell loss) and to give rise to lymphocytes and myeloerythroid cells that bore markers of the donor-injected cells.10,11 These genetic marking experiments established the fact that cells that can both self-renew and generate most (if not all) of the cell populations in the blood must exist in bone marrow. At the time, such cells were called pluripotent HSCs, a term later modified to multipotent HSCs.12,13 However, identifying stem cells in retrospect by analysis of randomly chromosome-marked cells is not the same as being able to isolate pure populations of HSCs for study or clinical use.

Achieving this goal requires markers that uniquely define HSCs. Interestingly, the development of these markers, discussed below, has revealed that most of the early spleen colonies visible 8 to 10 days after injection, as well as many of the later colonies, visible at least 12 days after injection, are actually derived from progenitors rather than from HSCs. Spleen colonies formed by HSCs are relatively rare and tend to be present among the later colonies.14,15 However, these findings do not detract from Till and McCulloch's seminal experiments to identify HSCs and define these unique cells by their capacities for self-renewal and multilineage differentiation.

While much of the original work was, and continues to be, performed in murine model systems, strides have been made to develop assays to study human HSCs. The development of Fluorescence Activated Cell Sorting (FACS) has been crucial for this field (see Figure 2.2). This technique enables the recognition and quantification of small numbers of cells in large mixed populations. More importantly, FACS-based cell sorting allows these rare cells (1 in 2000 to less than 1 in 10,000) to be purified, resulting in preparations of near 100% purity. This capability enables the testing of these cells in various assays.

Figure 2.2. Enrichment and purification methods for hematopoietic stem cells. Upper panels illustrate column-based magnetic enrichment. In this method, the cells of interest are labeled with very small iron particles (A). These particles are bound to antibodies that only recognize specific cells. The cell suspension is then passed over a column through a strong magnetic field which retains the cells with the iron particles (B). Other cells flow through and are collected as the depleted negative fraction. The magnet is removed, and the retained cells are collected in a separate tube as the positive or enriched fraction (C). Magnetic enrichment devices exist both as small research instruments and large closed-system clinical instruments.

Lower panels illustrate Fluorescence Activated Cell Sorting (FACS). In this setting, the cell mixture is labeled with fluorescent markers that emit light of different colors after being activated by light from a laser. Each of these fluorescent markers is attached to a different monoclonal antibody that recognizes specific sets of cells (D). The cells are then passed one by one in a very tight stream through a laser beam (blue in the figure) in front of detectors (E) that determine which colors fluoresce in response to the laser. The results can be displayed in a FACS-plot (F). FACS-plots (see figures 3 and 4 for examples) typically show fluorescence levels per cell as dots or probability fields. In the example, four groups can be distinguished: Unstained, red-only, green-only, and red-green double labeling. Each of these groups, e.g., green fluorescence-only, can be sorted to very high purity. The actual sorting happens by breaking the stream shown in (E) into tiny droplets, each containing 1 cell, that then can be sorted using electric charges to move the drops. Modern FACS machines use three different lasers (that can activate different set of fluorochromes), to distinguish up to 8 to 12 different fluorescence colors and sort 4 separate populations, all simultaneously.

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2. Bone Marrow (Hematopoietic) Stem Cells [Stem Cell Information]

By Andrew Brown

Spinal cord injury typically causes permanent paralysis and is currently a condition without a cure. Could stem cell therapy provide hope?

American actor and activist Christopher Reeve will be remembered for his leading role in the 1978 blockbuster movie Superman. Sadly, he will also be remembered as a man whose tremendously active life, both on and off screen, was shattered by a catastrophic injury that left him paralysed from the neck downwards a state in which he remained until he died in 2004.

In May 1995, during an equestrian competition, Reeve was thrown headfirst off his horse. The weight of his body was thrust through his spine, breaking two of the vertebrae in his neck and causing extensive damage to his spinal cordw1.

What happened during his accident at the level of blood, bones, cells and molecules to cause his life-long paralysis? And how might research into new treatments based on stem cells offer hope for people paralysed by spinal cord injury? Could it help them to regain some control over their bodies and their lives?

What is spinal cord injury?

Your spinal cord is an information highway connecting your brain to the rest of your body (figure 1). Injuries to it are usually caused by sudden trauma, such as that sustained in sports or car accidents, and result in dislocation and / or breakage of vertebrae, which rip into the spinal cord tissue, damaging or severing axons. Sensation and motor control are lost below the level of the injury (figure 2).

Multiple cell types die at or near the site of the spinal cord injury, due tosecondary effects of the trauma, such as changes in blood supply, immune responses and an increase in free radicals and excitatory neurotransmitters (see box on the secondary effects of spinal cord injury).

Figure 1: Anatomy and function of the spinal cord. Click on image to enlarge.

The spinal cord is a soft, jelly-like structure that extends from the base of the brain to the lower back (A). It is 38 to 43 cm long and, at its maximum width, is about as wide as a thumb. It sits in a hollow channel that runs through the spinal columns 33 stacked vertebrae (B).

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Spinal cord injury: do stem cells have the answer? | Science ...

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Lot of 5 Serious Skin Care Replicate Renew Plant Stem Cell ...

November 22, 2013

Brett Smith for redOrbit.com Your Universe Online

Scientists from the University of Granada in Spain have announced the development of artificial skin, grown from umbilical cord stem cells. The development could be a massive step forward for the treatment of burn victims or other patients who have suffered severe skin damage.

According to a report, published in the journal Stem Cells Translational Medicine, the research team wrote that they were able to use stem cells derived from the umbilical cord, also known as Wharton stem cells, to generate oral-mucosa or epithelia, two types of tissues needed to treat skin injuries.

The researchers said their novel technique is an improvement on conventional methods that can take weeks to generate artificial skin. To grow the artificial tissue, the study team used a biomaterial made of fibrin and agarose that they had previously designed and developed.

Creating this new type of skin using stem cells, which can be stored in tissue banks, means that it can be used instantly when injuries are caused, and which would bring the application of artificial skin forward many weeks, said study author Antonio Campos, professor of Histology at the University of Granada.

The development builds on previous work by the same team, which was heralded at the World Congress on Tissue Engineering held a few months ago in Seoul, South Korea. The celebrated work pointed to the potential for Wharton stem cells to be turned into epithelia cells.

Last month, a team of Italian scientists announced they had developed a similar method but in reverse. According to their paper in the journal Nature Communications, the team took skin cells from a mouse and reverse programmed them back into stem cells. These stem cells were then used to reduce damages to the nervous system of lab mice.

Our discovery opens new therapeutic possibilities for multiple sclerosis patients because it might target the damage to myelin and nerves itself, said study author Gianvito Martino, from the San Raffaele Scientific Institute in Milan, Italy.

This is an important step for stem cell therapeutics, said Dr. Timothy Coetzee, a lead researcher at the National MS Society who was not directly involved in the research. The hope is that skin or other cells from individuals with MS could one day be used as a source for reparative stem cells, which could then be transplanted back into the patient without the complications of graft rejection.

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Artificial Skin Grown In Lab Using Stem Cells - Science News ...

The breakthrough marks a major advance in treating kidney disease and more avenues in bioengineering human organs. Researchers published their findings in the journal Nature Cell Biology, following their success in making human skin cells form a functioning "mini-kidney" with a width of only a few millimeters.

During self-organization, different types of cells arrange themselves with respect to each other to create the complex structures that exist within an organ, in this case, the kidney, Professor Melissa Little of University of Queenslands Institute for Molecular Bioscience (IMB), who led the study, said in a statement. The fact that such stem cell populations can undergo self-organization in the laboratory bodes well for the future of tissue bioengineering to replace damaged and diseased organs and tissues.

While it may be a while until the process can be used in human trials, Little says it could be a major development in treating chronic kidney disease.

One in three Australians is at risk of developing chronic kidney disease, and the only therapies currently available are kidney transplant and dialysis, Little said. Only one in four patients will receive a donated organ, and dialysis is an ongoing and restrictive treatment regime.

The engineered kidney is a first for science.

"This is the first time anybody has managed to direct stem cells into the functional units of a kidney," Professor Brandon Wainwright, from the University of Queensland, told The Telegraph. "It is an amazing process it is like a Lego building that puts itself together."

Scientists were able to make the kidney by identifying genes that remained active and inactive during kidney development. They were then able to alter the genes into embryonic cells that allowed them to self-organize into the human organ.

"The [researchers] spent years looking at what happens if you turn this gene off and this one on," Wainwright said. "You can eventually coax these stem cells through a journey they [the cells] go through various stages and then think about being a kidney cell and eventually pop together to form a little piece of kidney."

Little predicts the stem cell kidneys could one day be used to make human kidney transplants, or a cluster of mini kidneys used to boost renal function in patients.

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Kidney Grown From Stem Cells For The First Time, Australian Scientists Call Breakthrough ‘An Amazing Process’