LOUISVILLE, Ky. -- Robert Waddell says he's glad the stem cells that healed him came from "a guy who was 50 years old" and not a human embryo.

As a Catholic, Waddell opposes the destruction of embryos and didn't want to rely on embryonic stem cells to cure his kidney disease. But he avoided this moral dilemma by getting bone marrow stem cells from a friend who donated a kidney as part of a University of Louisville study.

"It has nothing to do with embryonic stem cells," said Waddell, a 47-year-old father of four. "That made it a lot easier."

Recent strides in stem-cell research show adult stem cells to be ever-more-promising, many scientists say, quelling the controversy steeped in faith and science that has long surrounded embryonic stem cells.

In fact, University of Louisville researcher Scott Whittemore said the debate is almost moot.

"Realistically, (many scientists don't use) the types of stem cells that are so problematic anymore," he said, adding that adult stem cells can now be reprogrammed to behave like embryonic stem cells. "The field has moved so fast."

In addition to these genetically reprogrammed adult cells - known as induced pluripotent stem cells or iPS cells - scientists are on the cusp of being able to turn one type of cell into another in the body without using stem cells at all. They shared some of the latest research last week at the annual International Society for Stem Cell Research in Vancouver.

"IPS cells overcame the main ethical issues," namely the use of embryos some Americans consider sacred human life, said Brett Spear, a professor of microbiology, immunology and molecular genetics at the University of Kentucky who uses iPS cells to model liver disease.

But other scientists argue that embryonic stem cell research remains important.

Dr. George Daley, director of the stem cell transplant program at Boston Children's Hospital and past president of the research society, said embryonic cells are a tool in the search for cures.

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Stem-cell advances may quell ethics debate

At Novartiss research lab in Cambridge, Massachusetts, a large incubator-like piece of equipment is helping give birth to a new era of psychiatric drug discovery. Inside it, bathed in soft light, lab plates hold living human stem cells; robotic arms systematically squirt nurturing compounds into the plates. Thanks to a series of techniques perfected over the last few years in labs around the world, such stem cellscapable of developing into specialized cell typescan now be created from skin cells. When stem cells derived from people with, say, autism or schizophrenia are grown inside the incubator, Novartis researchers can nudge them to develop into functioning brain cells by precisely varying the chemicals in the cell cultures.

Theyre not exactly creating schizophrenic or autistic neurons, because the cells arent working within the circuitry of the brain, but for drug-discovery purposes its the next best thing. For the first time, researchers have a way to directly examine in molecular detail whats going wrong in the brain cells of patients with these illnesses. And, critically for the pharmaceutical company, there is now a reliable method of screening for drugs that might help. Do the neurons look different from normal ones? Is there a flaw in the way they form connections? Could drugs possibly correct the abnormalities? The answer to each of these questions is a very preliminary yes.

The technique is so promising that Novartis has resumed trying to discover new psychiatric drugs after essentially abandoning the quest. Whats more, its been introduced at a time when knowledge about the genetics behind brain disorders is expanding rapidly and other new tools, including optogenetics and more precise genome editing (see Neurosciences New Toolbox), are enabling neuroscientists to probe the brain directly. All these developments offer renewed hope that science could finally deliver more effective treatments for the millions of people beset by devastating brain disorders.

A revival in psychiatric drug development is badly needed: there hasnt been a breakthrough medicine for any of the common mental illnesses, including schizophrenia, bipolar disorder, or severe depression, in roughly 50 years. From the late 1940s through the 1960s, a series of serendipitous discoveries, beginning with the finding that lithium could help bipolar patients, transformed the treatment of the mentally ill. It became possible to quiet the hallucinations and delusions of schizophrenia and offer a drug to the severely depressed. The sudden availability of pharmacological relief transformed psychiatry and played a role in closing down many of the mammoth mental hospitals of the era. But then, almost as suddenly as it had started, the revolution stalled.

Many of the drugs discovered in the 1950s and 1960s are still the most effective treatments available for schizophrenia, anxiety disorders, and depression. But while these medications have improved the lives of some patients, they are ineffective for others, and they are woefully inadequate in treating many of the worst symptoms. Whats more, the drugs can have severe side effects.

Take schizophrenia, for example. Existing antipsychotic drugs can make the hallucinations and delusions disappear, but they dont improve the so-called negative symptomsthe disruption of emotions such as pleasure, which can leave people uninterested in communicating or even in living. Existing drugs also have no effect on the way schizophrenia can impair concentration, decision-making, and working memory (critical in such tasks as language comprehension). These debilitating cognitive problems make it impossible for people to work and difficult for them even to make the seemingly simple logical choices involved in everyday life. Insidiously, such symptoms can strike high-performing individuals, often in their late teens. People dont understand, says Guoping Feng, a professor of neuroscience at MIT who studies the neural basis of psychiatric disorders. They ask, once a patient is given antipsychotic medicine, Why cant you go to work? But [those with schizophrenia] cant work because they dont have cognitive functions, they dont have normal executive functions. And there are no drugs for this. On top of that are the side effects of antipsychotic medicines, which can include Parkinsons-like movement disorders, dramatic weight gain, or a potentially deadly loss of white blood cells. In short, the illness destroys many patients lives.

We were led down a path that said depression is about being a quart low in serotonin, and schizophrenia means you have a bit too much dopamine on board. But that just isnt how the brain works. The brain isnt a bowl of soup.

Finally, many people with brain disorders are simply not helped at all by available drugs. Antidepressants work well for some people but do nothing for many others, and there are no effective drug treatments for the social disabilities or repetitive behaviors caused by autism.

Overall, neuropsychiatric illness is a leading cause of disability. According to the National Institute of Mental Health (NIMH) in Rockville, Maryland, 26 percent of American adults suffer from a diagnosable mental disorder in any given year. Severe depression, the most common of these disorders, is the leading cause of disability in the U.S. for individuals between 15 and 44. Around 1 percent of the American population suffers from schizophrenia; one in 68 American children is diagnosed with an autism spectrum disorder.

Though the need for better treatments is unquestionable, drug companies had until very recently simply run out of good ideas. The drugs developed in the 1950s and 1960s were discovered by accident, and no one knew how or why they worked. In the subsequent decades, drug researchers reverse-engineered the medications to identify the brain molecules that the drugs acted on, such as dopamine and serotonin. In retrospect, however, scientists now realize that while tweaking the levels of these chemicals addressed some symptoms of psychiatric disorders, it was a crude strategy that ignored the biological mechanisms underlying the illnesses.

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Shining Light on Madness

Poway, CA (PRWEB) June 20, 2014

Vet-Stem, Inc. announced that another patent has issued under its exclusive worldwide license with Artecel, Inc. and with The University of California. This patent covers compositions of adipose tissue-derived stem cells that can differentiate into many types of tissues include cartilage, bone, nerve, kidney, heart and skin. This patent will provide coverage for the on-going commercial and development programs at Vet-Stem.

This new patent adds to the other patents in the Vet-Stem portfolio that cover compositions and methods of production of regenerative cells from adipose tissue for many diseases in humans and animals. Vet-Stem has exclusive worldwide rights for veterinary use of these patents (over 50 issued and 70 pending patents) which improves the companys intellectual property position in this rapidly developing field.

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. In the last decade over 10,000 animals including horses, dogs, cats, and some exotics have been treated using Vet-Stems services.

Intellectual property rights are key assets in these markets and our investments in the area over the last decade have created tremendous value for our shareholders, said Robert Harman, DVM, MPVM, CEO and Founder of Vet-Stem. We need to do everything possible to protect and grow the market that we are creating in Regenerative Veterinary Medicine by providing the highest quality control in the industry. The value of this technology has increased greatly since the founding of the company in 2002 by providing clear evidence of the therapeutic activity and safety of these stem cells.

Vet-Stem researchers have been authors on 11 peer-reviewed papers including the first blinded, controlled, multicenter study of adipose-derived stem cells for chronic osteoarthritis in the canine hip joint, and the first multicenter clinical study of adipose-derived stem cells for chronic osteoarthritis in the canine elbow. Vet-Stem is actively investigating stem cell therapy for immune-mediated and inflammatory disease, as well as organ disease and failure.

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. The company holds exclusive licenses to over 50 patents including world-wide veterinary rights for use of adipose derived stem cells. 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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Canadian Patent for Adipose Stem Cells Issued Under Vet-Stem License

NEW YORK (CNNMoney)

No need to go that far.

It turns out, the best kind of anti-aging treatment is inside one's own body, and the rich are taking advantage of it, exploring the latest research in new technologies, genome mapping and stem cell treatments.

Among them is Oracle billionaire Larry Ellison, a large investor of the Ellison Medical Foundation, which supports research exploring the biology that underlies aging and age-related diseases. And there's billionaire Peter Nygrd, who says he wants to live forever (or die trying), and has suggested he's found the keys to immortality in stem cell research.

Some doctors agree that stem cells are a key part of chasing youth.

"If you're a wealthy guy and haven't stored your stem cells, I think you're a total idiot," said Dr. Lionel Bissoon, a New York City physician who sees a number of stressed out, wealthy patients.

Related: It's expensive being rich

They usually come to him with similar problems: "Fatigue, belly fat, erectile dysfunction, tiring very quickly ... all very common with my patients from Wall Street," Bissoon said. The short-term solution to those ailments, he says, is testosterone replacement -- which is relatively affordable at a few hundred dollars a pop -- and IV nutrition.

For the long term he recommends stem cell storage, which works as a sort of rainy day insurance. The cells are extracted, preferably when the patient is on the younger side -- around 30 is said to be a good age -- and can then be used to boost an immune system or help to rebuild damaged organs later.

Dr. Dipnarine Maharaj stores cells at his South Florida Bone Marrow Stem Cell Transplant Institute in Boynton Beach, Fla.

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Can enough money buy you eternal youth?

Stemologica
Researchers have verified that when included in our skin creams, the Uttwiler Sptlauber Swiss apple stem cells will communicate with you have skin #39;s stem ce...

By: Jordan Kaleb

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Stemologica - Video

H-E-B's private label skin care line is the retailers Beauty Pick of the Month.

The formula for EverVescence by H-E-B includes Uttwiler Spatlauber Swiss Apples, which contain stem cells that help reduce the appearance of fine lines, wrinkles and tired skin.

The line includes: Redefining Eye Cream, Redefining Face Serum and Facial Moisturizer with SPF 15.

As the beauty pick of the month, the line is promoted on heb.com and social media.

The Beauty Pick of the Month is also reviewed by members of H-E-B's beauty panel, which includes H-E-B's employees as well as beauty bloggers.

Among the reviews:

"The eye cream is like a spa treatment with a cooling effect that sinks in and feels fabulous, wrote "Cheryl," online editor for heb.com. Now I can pick up my skincare products at my HEB.

Meanwhile, Liz, H-E-Bs digital marketing manager, said she would recommend all three items to others:

"I used all three as directed and found my skin was softer, she said. The smell was light and not unpleasant like other products I have tried. The products did not irritate my sensitive skin.

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H-E-B promotes store brand skin care line

Sarasota, FL (PRWEB) June 12, 2014

Nebulized Pure PRP may offer COPD sufferers a less expensive and an effective alternative to stem cell therapy. When normal injury occurs, platelets are stimulated to release growth factors, cytokines and other immune system components in what is called the inflammatory phase of healing. In the lungs, platelets can adhere to injured or inflamed endothelial cells where they start the healing process. It is believed that by increasing the number of platelets in the lungs through this method, it is possible to decrease inflammation and accelerate the healing process in the lungs. Platelets are vehicles for the delivery of growth factors (PDGF, TGF-, IGF, EGF, VEGF) that induce proliferation of fibroblasts, osteoblasts and endothelial cells, promoting and accelerating healing of hard and soft tissues.

Autologous Platelet Rich Plasma also contains fibrin, fibronectin and vitronectin that act as cell adhesion molecules for lung epithelial migration. Autologous Platelet Rich Plasma treatment has been evaluated in various medical disciplines including orthopaedics, wound healing, neurosurgery, dentistry as well as cosmetic, plastic and cardiothoracic surgery. Nebulized Pure PRP treatment holds much promise and is being researched for its applications.

This new medical advance can bring effective and affordable healthcare to many patients with COPD. It is also attractive because the patients own blood is used thus, limiting the potential for disease transmission.

Our key product differentiation is to enable the Pure PRP treatment to be applied to patients who are suffering from COPD. COPD is the most dangerous disease in the elderly, affecting more than 200 million people across the globe. COPD is considered to be the cause of about 3 million deaths annually. This is a life-threatening disease caused by many reasons such as smoking, pollution, dust, irritants, genetic disorders, etc. It is associated with the excess production of sputum and an inflammation which obstructs the airways and results in breathing problems.

Though there is no cure for COPD, the condition can be controlled with the help of treatments. Stem cell therapy which has proved to be one of the most successful treatments for many chronic health conditions like heart disease, stroke, osteoporosis, etc., has given a ray of hope in favor of COPD. Stem cells are known for their regenerative properties which help in the development of the tissues and blood cells. These cells are of two types: embryonic stem cells and adult stem cells. Embryonic stem cells can be derived from blastocyst which is a type of embryo; whereas adult stem cells are found in the bone marrow, skin, umbilical cord, placenta and many other tissues. Embryonic stem cells are derived and are grown in cell culture for research and development. But adult stem cells, once removed from the body, divide with great difficulty which makes the treatment difficult to perform. The stem cells are either from the person itself who needs it which is known as autologous stem cell or they can be received from a donor which is known as allogeneic stem cell.

Cells donated by the donor may or may not be accepted by the bodys immune system. Hence, using ones own stem cells reduces the chances of rejection. In COPD, the tissues and cells of the lungs are destroyed, which causes various types of complications. Hence, with the help of stem cell therapy, the destroyed or damaged cells can be regenerated and new lung tissues can be formed. According to the procedure followed by the International Stem Cell Institute (ISCI); San Diego, California, adipose tissue is removed from the patient and is processed with a combination of platelet rich plasma which contains growth factors that help in the process of cell multiplication and development. This helps in COPD treatment as whenever the lungs need repair, about 80% of the stem cells reach the repairing site through the circulatory system. When the blood passes through the lungs, stem cells get trapped in the space where there is damage. The stem cells then start multiplying and repairing the tissue. The recovery does not take place immediately, but improvement can be noticed in 3 to 6 months. It helps in the suppression of inflammation, improves breathing and cures many pulmonary complications. Our Nebulized Pure PRP System aims to support this proposition to treat COPD patients. Treatments run about $1,000 and insurance does not currently pay for this treatment.

Contact our office at (941) 330-8553 to find out more about how Nebulized Pure PRP can offer you relief from symptoms of COPD. Also we are at http://advancedwellness.us/blog2/nebulized-platelet-rich-plasma-prp-for-asthma-copd-and-systemic-growth-effects-in-athletics/

Click to learn more about this treatment.

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New Stem Cell Based Treatment for COPD; Nebulized Pure PRP System Uses Blood Growth Factors That Can Trigger Healing ...

NBC News -- Researchers have grown part of an eye in a lab dish, using a type of stem cell made from a piece of skin.

They said the little retina started growing and developing on its own an important step towards creating custom-tailored organs in the lab.

We have basically created a miniature human retina in a dish that not only has the architectural organization of the retina but also has the ability to sense light," said M. Valeria Canto-Soler, an assistant professor of ophthalmology at the Johns Hopkins University School of Medicine.

The team used cells called induced pluripotent stem cells, or iPS cells, which are immature stem cells whose powers resemble those of embryonic stem cells they can morph into any cell type in the body.

Theyre made by tricking an ordinary cell, like a skin cell, into reverting back into embryonic mode. Then the researchers activate genes to get the cell to redirect itself into forming the desired cells in this case cells of the retina.

To the surprise of the researchers, the cells started developing as if they were in a growing human embryo.

"We knew that a 3-D cellular structure was necessary if we wanted to reproduce functional characteristics of the retina, but when we began this work, we didn't think stem cells would be able to build up a retina almost on their own. In our system, somehow the cells knew what to do, Canto-Soler said in a statement.

The experiment may ultimately lead to technologies that restore vision in people with retinal diseases, she added.

Tests showed the cells responded to light, the team reported in the journal Nature Communications. "Is our lab retina capable of producing a visual signal that the brain can interpret into an image? Probably not, but this is a good start," Canto-Soler said.

Other teams have used iPS cells to make a piece of human liver and are using them to study a range of human diseases.

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Eye in a Dish: Researchers Make Retina From Stem Cells

Jun 06, 2014 This is a representation of hydrogel polymers (straight lines) trapping stem cells (light-colored figures) and water (blue). Credit: Michael Osadciw/ University of Rochester.

When stem cells are used to regenerate bone tissue, many wind up migrating away from the repair site, which disrupts the healing process. But a technique employed by a University of Rochester research team keeps the stem cells in place, resulting in faster and better tissue regeneration. The key, as explained in a paper published in Acta Biomaterialia, is encasing the stem cells in polymers that attract water and disappear when their work is done.

The technique is similar to what has already been used to repair other types of tissue, including cartilage, but had never been tried on bone.

"Our success opens the door for manyand more complicatedtypes of bone repair," said Assistant Professor of Biomedical Engineering Danielle Benoit. "For example, we should now be able to pinpoint repairs within the periosteumor outer membrane of bone material."

The polymers used by Benoit and her teams are called hydrogels because they hold water, which is necessary to keep the stem cells alive. The hydrogels, which mimic the natural tissues of the body, are specially designed to have an additional feature that's vital to the repair process; they degrade and disappear before the body interprets them as foreign bodies and begins a defense response that could compromise the healing process.

Because stem cells have the unique ability to develop into many different types of cells, they are an important part of the mechanism for repairing body tissue. At present, unadulterated therapeutic stem cells are injected into the bone tissue that needs to be repaired. Benoit believed hydrogels would allow the stem cells to finish the job of initiating repairs, then leave before overstaying their welcome.

The research team tested the hypothesis by transplanting cells onto the surface of mouse bone grafts and studying the cell behavior both in vivoinside the animaland in vitrooutside the body. They started by removing all living cells from donor bone fragments, so that the tissue regeneration could be accomplished only by the stem cells.

In order to track the progress of the research, the stem cells were genetically modified to include genes that give off fluorescence signals. The bone material was then coated with the hydrogels, which contained the fluorescently labeled stem cells, and implanted into the defect of the damaged mouse bone. At that point, the researchers began monitoring the repair process with longitudinal fluorescence to determine if there would be an appreciable loss of stem cells in the in vivo samples, as compared to the static, in vitro, environments. They found that there was no measurable difference between the concentrations of stem cells in the various samples, despite the fact that the in vivo sample was part of a dynamic environmentwhich included enzymes and blood flowmaking it easier for the stem cells to migrate away from the target site. That means virtually all the stem cells stayed in place to complete their work in generating new bone tissue.

"Some types of tissue repair take more time to heal than do others," said Benoit. "What we needed was a way to control how long the hydrogels remained at the site."

Benoit and her team were able to manipulate the time it took for hydrogels to dissolve by modifying groups of atomscalled degradable groupswithin the polymer molecules. By introducing different degradable groups to the polymer chains, the researchers were able to alter how long it took for the hydrogels to degrade.

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Better tissue healing with disappearing hydrogels

13 hours ago Microscope And Digital Camera. Credit: Richard Wheeler/ Wikipedia CC BY-SA 3.0

Case Western Reserve researchers have discovered landmarks within pluripotent stem cells that guide how they develop to serve different purposes within the body. This breakthrough offers promise that scientists eventually will be able to direct stem cells in ways that prevent disease or repair damage from injury or illness. The study and its results appear in the June 5 edition of the journal Cell Stem Cell.

Pluripotent stem cells are so named because they can evolve into any of the cell types that exist within the body. Their immense potential captured the attention of two accomplished faculty with complementary areas of expertise.

"We had a unique opportunity to bring together two interdisciplinary groups," said co-senior author Paul Tesar, PhD, Assistant Professor of Genetics and Genome Sciences at CWRU School of Medicine and the Dr. Donald and Ruth Weber Goodman Professor.

"We have exploited the Tesar lab's expertise in stem cell biology and my lab's expertise in genomics to uncover a new class of genetic switches, which we call seed enhancers," said co-senior author Peter Scacheri, PhD, Associate Professor of Genetics and Genome Sciences at CWRU School of Medicine. "Seed enhancers give us new clues to how cells morph from one cell type to another during development."

The breakthrough came from studying two closely related stem cell types that represent the earliest phases of developmentembryonic stem cells and epiblast stem cells, first described in research by Tesar in 2007. "These two stem cell types give us unprecedented access to the earliest stages of mammalian development," said Daniel Factor, graduate student in the Tesar lab and co-first author of the study.

Olivia Corradin, graduate student in the Scacheri lab and co-first author, agrees. "Stem cells are touted for their promise to make replacement tissues for regenerative medicine," she said. "But first, we have to understand precisely how these cells function to create diverse tissues."

Enhancers are sections of DNA that control the expression of nearby genes. By comparing these two closely related types of pluripotent stem cells (embryonic and epiblast), Corradin and Factor identified a new class of enhancers, which they refer to as seed enhancers. Unlike most enhancers, which are only active in specific times or places in the body, seed enhancers play roles from before birth to adulthood.

They are present, but dormant, in the early mouse embryonic stem cell population. In the more developed mouse epiblast stem cell population, they become the primary enhancers of their associated genes. As the cells mature into functional adult tissues, the seed enhancers grow into super enhancers. Super enhancers are large regions that contain many enhancers and control the most important genes in each cell type.

"These seed enhancers have wide-ranging potential to impact the understanding of development and disease," said Stanton Gerson, MD, Asa & Patricia Shiverick and Jane Shiverick (Tripp) Professor of Hematological Oncology and Director of the National Center for Regenerative Medicine at Case Western Reserve University. "In the stem cell field, this understanding should rapidly enhance the ability to generate clinically useful cell types for stem cell-based regenerative medicine."

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Stem cells hold keys to body's plan

13 hours ago Directed Network Wiring, a new method to simplify the study of protein networks, is illustrated. Credit: Shohei Koide/University of Chicago

Proteins are responsible for the vast majority of the cellular functions that shape life, but like guests at a crowded dinner party, they interact transiently and in complex networks, making it difficult to determine which specific interactions are most important.

Now, researchers from the University of Chicago have pioneered a new technique to simplify the study of protein networks and identify the importance of individual protein interactions. By designing synthetic proteins that can only interact with a pre-determined partner, and introducing them into cells, the team revealed a key interaction that regulates the ability of embryonic stem cells to change into other cell types. They describe their findings June 5 in Molecular Cell.

"Our work suggests that the apparent complexity of protein networks is deceiving, and that a circuit involving a small number of proteins might control each cellular function," said senior author Shohei Koide, PhD, professor of biochemistry & molecular biophysics at the University of Chicago.

For a cell to perform biological functions and respond to the environment, proteins must interact with one another in immensely complex networks, which when diagrammed can resemble a subway map out of a nightmare. These networks have traditionally been studied by removing a protein of interest through genetic engineering and observing whether the removal destroys the function of interest or not. However, this does not provide information on the importance of specific protein-to-protein interactions.

To approach this challenge, Koide and his team pioneered a new technique that they dub "directed network wiring." Studying mouse embryonic stem cells, they removed Grb2, a protein essential to the ability of the stem cell to transform into other cell types, from the cells. The researchers then designed synthetic versions of Grb2 that could only interact with one protein from a pool of dozens that normal Grb2 is known to network with. The team then introduced these synthetic proteins back into the cell to see which specific interactions would restore the stem cell's transformative abilities.

"The name, 'directed network wiring,' comes from the fact that we create minimalist networks," Koide said. "We first remove all communication lines associated with a protein of interest and add back a single line. It is analysis by addition."

Despite the complexity of the protein network associated with stem cell development, the team discovered that restoring only one interactionbetween Grb2 and a protein known as Ptpn11/Shp2 phosphatasewas enough to allow stem cells to again change into other cell types.

"We were really surprised to find that consolidating many interactions down to a single particular connection for the protein was sufficient to support development of the cells to the next stage, which involves many complicated processes," Koide said. "Our results show that signals travel discrete and simple routes in the cell."

Koide and his team are now working on streamlining directed network wiring and applying it to other areas of study such as cancer. With the ability to dramatically simplify how scientists study protein interaction networks, they hope to open the door to new research areas and therapeutic approaches.

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New method reveals single protein interaction key to embryonic stem cell differentiation

19 hours ago Fig. 1: Pluripotent stem cells enable planarians to achieve extraordinary feats of regeneration. (A) Planarians are able to re-grow an entire head in a matter of a few days. (B) The stem cells and their early offspring can be found almost all over the worms body. During regeneration, when a lot of new tissue has to be produced, they are able to generate a wide variety of cell types. The cell nuclei are marked in blue. Tissue-specific markers are marked in red, green and white. Credit: Max Planck Institute for Molecular Biomedicine /Bartscherer

Planarians are known as masters of regeneration: they can re-build any part of their bodies after amputation. This ability relies on a large number of pluripotent stem cells. To further investigate the mechanisms that enable planarians to maintain their stem cell pool over generations, scientists have now established a method for analysing the composition of planarian stem cells and the turnover of their proteins. They discovered a protein that is not only required for the maintenance of the stem cell pool in planarians, but might also be active in the pluripotent stem cells of mammals.

Of earthworms and flatworms

Everyone knows the myth about earthworms: if you cut them in half, you get two worms. Nothing could be further from the truth, alas. However, if the earthworm is replaced by a flatworm, the two parts can survive these childish experiments. What's more, be it skin, intestine or brain, the body part lost through cutting will simply grow again in a matter of days. The creatures involved here are planarians[1], a class of flatworms that are so flat that they need neither lungs nor a heart to take in and distribute oxygen in their bodies. So simple and yet so ingenious? It would appear so. Regeneration studies involving these animals have shown that a dismembered planarian can generate several hundred tiny animals, hence they could "almost be called immortal under the edge of a knife" (Dalyell, 1814). The astonishing aspect here is that both the blueprint and construction material for the regeneration process must be contained in each of the fragments: a small piece of tail, for example, becomes a complete worm under the animal's own strength and using existing resources.

Not the preserve of youth: pluripotency also available in adults

So where do the components needed to rebuild the cellular structures come from? In their search for the answer to this question, scientists have a population of small cells in their sights, namely the approximately five-micrometre-long neoblasts. These cells are found almost everywhere in the planarian body and behave like stem cells: they divide, renew and can form the different cell types that have been lost as a result of amputation (Fig. 1). When the planarian loses a body part or discards its tail for reproduction, the neoblasts are reactivated and migrate to the wound. They divide there and their offspring form a blastema, in which as a result of interplay between various extra- and intra-cellular factors important differentiation and patterning processes take place. Thanks to these processes, in turn, complex structures like the brain are formed. If the neoblasts are eliminated through radiation, for example, the planarian loses its ability to regenerate and dies within a few weeks. The fact that, following transplantation into an irradiated, neoblast-free worm, a single neoblast can produce all cell types and enable the host worm to regain its ability to regenerate shows that at least some neoblasts are pluripotent [2]. In healthy mammals, pluripotency, that is the ability of one cell to produce any given cell type found in an organism, e.g. muscle, nerve or pancreas cells, only arises in the early embryonic stage. Therefore, stable pluripotency in the adult organism is something special but not impossible as long as mechanisms exist for conserving this characteristic as is clearly the case with the planarians.

An in-vivo Petri dish for pluripotent stem cells

The preservation of pluripotency has been an important topic in stem cell research for years, and has mostly been examined up to now using isolated embryonic stem cells. Important transcription factors that can induce and preserve pluripotency were discovered in the course of this research. So what can planarians contribute to the current research if their stem cells cannot be cultivated and reproduced outside of the body? This is precisely where the strength of the planarians as a model system in stem cell research lies: the combination they can offer of a natural extracellular environment and pluripotent stem cells. Whereas cultivated stem cells are normally taken out of their natural environment and all important interactions with neighbouring cells and freely moving molecules are interrupted as a result, the stem cells in planarians can be observed and manipulated under normal conditions in vivo. Therefore, planarians are of interest as "in-vivo Petri dishes" for stem cells, in which not only their mechanisms for preserving pluripotency can be studied, but also their regulation and contribution to regeneration.

A venerable old worm meets ultra-modern next-generation technologies

Although planarians have been renowned as masters of regeneration and research objects for generations, they have undergone a genuine explosion in research interest in recent years. In particular, the possibility of switching off specific genes through RNA interference (RNAi) and the availability of the genome sequence of Schmidtea mediterranea, a planarian species which is especially good at regenerating itself, have contributed to this surge in interest. With the development of modern sequencing procedures, that is 'next generation sequencing', gene expression profiles that provide information about the specific genes activated in particular cells or tissues at particular points in time can now be produced on a large scale. Hence, it is possible to examine which messenger RNAs (mRNAs) are produced that act as molecular templates for the production of proteins. For example, hundreds of these mRNAs are produced after the amputation of a worm's head and their proteins provide potential regulators of the regeneration process [3; 4]. However, the real work only starts here: the extent to which the presence of a particular mRNA also reflects the volume of protein that is active in the cell remains to be determined. It is mainly the proteins in the form of enzymes, signalling molecules and structural elements, and not their mRNAs, that ultimately control the majority of cellular processes. In addition, their production using mRNA templates and their lifetime are precisely regulated processes and the frequency with which an mRNA arises cannot provide any information about these processes. The time has come, therefore, to develop experimental approaches for planarians that extend beyond gene expression analysis and lend greater significance to the subsequent regulatory processes.

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How planarians maintain their stem cell pools over generations

Boston, MA (PRWEB) June 03, 2014

Today, Dr. James L. Sherley, the Director of Bostons Adult Stem Cell Technology Center, LLC (ASCTC) described a new technology for identification of new drug candidates that are toxic to adult stem cell cells in the human body. The new AlphaSTEM technology is the first of its kind to address a long-standing unmet need in the pharmaceutical industry.

Dr. Sherley presented the AlphaSTEM technology at the 7th Annual Massachusetts Life Sciences Innovation Day (MALSI Day 2014; http://www.mattcenter.org/malsi-day-2014/home.html) at the Harvard Club of Boston. ASCTC is one of a select number of start-up companies invited to present posters on their newest innovative biotechnologies at the all day event, which features the best and brightest life sciences innovations of the year.

Just as adult stem cells are crucial for life and normal organ function, their safety is crucial for successful treatment with new drugs. Even if a new drug has high activity against a disease or disorder; it will not be an effective treatment, if it is also too toxic to adult stem cells.

Adult stem cells are found in all renewing tissues and organs of the human body, like hair, skin, liver, and even the brain. They are responsible for replacing old mature tissue cells with new young cells. They are also essential cells for repairing injured tissues and wounds.

Some drugs are known to harm adult stem cells. Examples of these are many cancer drugs. Cancer drugs are often administered at the highest doses at which patients can tolerate the adverse effects of the drugs on adult stem cells. ASCTCs AlphaSTEM technology could accelerate discovery of better cancer drugs with less adult stem cell toxicity.

The major application proposed for the new AlphaSTEM technology is use by pharmaceutical companies to identify adult stem cell-toxic drugs before initiating clinical trials with them or entering the marketplace. Drug failure in clinical trials due to safety concerns is a major unrecovered cost of drug development. Chronic adult stem cell toxicity that now may go undetected until after marketing can result in tragic deaths for patients and catastrophic injury liabilities for the responsible drug companies. The Merck drug Vioxx is an example of such an unfortunate mishap.

The problem faced by the Food and Drug Administration (FDA) and the pharmaceutical industry is how to monitor drug effects on adult stem cells, when the cells are difficult to identify, isolate, produce, and count. The solution presented by ASCTC was a computer simulation approach based on the universal tissue cell production properties of adult stem cells.

ASCTC partnered with AlphaSTAR Corporation, a leading global provider of simulation technologies, to develop the AlphaSTEM software program that can simulate the culture multiplication of adult tissue stem cells found in any human tissue. AlphaSTEM technology not only has the power to detect drug toxicity against adult stem cells, but also against other specialized types of tissue cells specifically.

Director Sherley predicted that the introduction of AlphaSTEM technology into the pharmaceutical industry would have many immediate benefits. With relatively inexpensive detection of drugs destined to fail in expensive clinical trials, the new technology could save billions of currently wasted dollars, reducing overall drug development costs in the U.S. by as much as 20%. These savings could accelerate the rate of arrival of new effective drugs to patients by a comparable reduction in time. AlphaSTEM technology may also reduce the occurrence of drugs thought safe, but which actual have a lurking toxicity that emerges as lethal to some patients with wider and longer use.

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The Adult Stem Cell Technology Center, LLC Announces New Technology for Preventing Catastrophic Adult Stem Cell ...

"It's a tiny wee finger prick test," says senior nurse Patsy Scouse to calm the nervous first-time donor having his hemoglobin levels tested at a blood donation centre in Edinburgh.

The Scottish National Blood Transfusion Service receives donations from about four percent of the UK's population. Currently, stocks are stable, although the service is always trying to recruit new donors.

The collection may take place in a clinical environment, the nurse says, but the clinic "wants this experience, especially for first-time donors, to be really positive so they can go out and feel they've done a really good thing."

But the service is also working on potential new technologies to secure blood supplies in the future, including "artificial blood."

Mass-produced and clean

Mark Turner, medical director of the Blood Transfusion Service, is looking into how blood could be synthesized in the future.

"We've known for some time that it's possible to produce red blood cells from so called adult stem cells, but you can't produce large amounts of blood in that way because of the restrictive capacity of those cells to proliferate," he explains. What scientists can do, he adds, is to derive pluripotent stem cells - stem cell lines - either from embryos or from adult tissue.

These cells are processed in the laboratory to produce larger numbers of cells, Turner told DW.

"It may be possible in due course to manufacture blood on a very large scale, but we're a very long way from that at the present time," he says. "At the moment, our focus is on trying to achieve production of red blood cells which are of the right kind of quality and safety, that they would be fit for human trials."

From the lab to clinical trials

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Artificial blood made from human stem cells could plug the donations hole

Scientists have a new way to repair teeth, and they say their concept - using laser light to entice the body's own stem cells into action - may offer enormous promise beyond just dentistry in the field of regenerative medicine.

The researchers used a low-power laser to coax dental stem cells to form dentin, the hard tissue similar to bone that makes up most of a tooth, demonstrating the process in studies involving rats and mice and using human cells in a laboratory.

They did not regenerate an entire tooth in part because the enamel part was too tricky. But merely getting dentin to grow could help alleviate the need for root canal treatment, the painful procedure to remove dead or dying nerve tissue and bacteria from inside a tooth, they said.

"I'm a dentist by training. So I think it has potential for great impact in clinical dentistry," researcher Praveen Arany of the National Institute of Dental and Craniofacial Research, part of the U.S. National Institutes of Health, said on Friday.

Arany expressed hope that human clinical trials could get approval in the near future.

"Our treatment modality does not introduce anything new to the body, and lasers are routinely used in medicine and dentistry, so the barriers to clinical translation are low," added Harvard University bioengineering professor David Mooney.

"It would be a substantial advance in the field if we can regenerate teeth rather than replace them." Using existing regeneration methods, scientists must take stem cells from the body, manipulate them in a lab and put them back into the body.

This new technique more simply stimulates action in stem cells that are already in place. Scientists had long noticed that low-level laser therapy can stimulate biological processes like rejuvenating skin and stimulating hair growth but were not sure of the mechanisms.

Arany noted the importance of finding the right laser dose, saying: "Too low doesn't work and too high causes damage."

First published May 30 2014, 2:24 PM

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Bright Idea: Scientists Use Laser Lights to Regrow Teeth

PUBLIC RELEASE DATE:

30-May-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. For many scientists, the clinical promise of stem cells has been dampened by very real concerns that the immune system will reject the transplanted cells before they could render any long-term benefit. Previous research in mice has suggested that even stem cells produced from the subject's own tissue, called iPS cells, can trigger an immune attack.

Now researchers at the Stanford University School of Medicine have found that coaxing iPS cells in the laboratory to become more-specialized progeny cells (a cellular process called differentiation) before transplantation into mice allows them to be tolerated by the body's immune system.

"Induced pluripotent stem cells have tremendous potential as a source for personalized cellular therapeutics for organ repair," said Joseph Wu, MD, PhD, director of the Stanford Cardiovascular Institute. "This study shows that undifferentiated iPS cells are rejected by the immune system upon transplantation in the same recipient, but that fully differentiating these cells allows for acceptance and tolerance by the immune system without the need for immunosuppression."

The findings are described in a paper to be published online May 30 in Nature Communications. Wu is senior author of the paper. Postdoctoral scholars Patricia Almeida, PhD, and Nigel Kooreman, MD, and assistant professor of medicine Everett Meyer, MD, PhD, share lead authorship.

In a world teeming with microbial threats, the immune system is a necessary watchdog. Immune cells patrol the body looking not just for foreign invaders, but also for diseased or cancerous cells to eradicate. The researchers speculate that the act of reprogramming adult cells to pluripotency may induce the expression of cell-surface molecules the immune system has not seen since the animal (or person) was an early embryo. These molecules, or antigens, could look foreign to the immune system of a mature organism.

Previous studies have suggested that differentiation of iPS cells could reduce their tendency to inflame the immune system after transplantation, but this study is the first to closely examine, at the molecular and cellular level, why that might be the case.

"We've demonstrated definitively that, once the cells are differentiated, the immune response to iPS-derived cells is indistinguishable from its response to unmodified tissue derived from elsewhere in the body," said Kooreman.

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Coaxing iPS cells to become more specialized prior to transplantation cuts rejection risk

Ranking among the X-Men probably isn't all that it's cracked up to be, but who wouldn't want their uncanny ability to regenerate lost bone or tissue? New research into tooth repair and stem cell biology, from a cross-institution team led by David Mooney of Harvard's Wyss Institute, may bring such regeneration one step closer to reality or at the very least, give us hope that we can throw away those nasty dentures.

The researchers employed a low-power laser to trigger human dental stem cells to form dentin, a hard bone-like tissue that is one of four major components of teeth (the others being enamel, pulp, and cementum). This kind of low-level light therapy has previously been used to remove or stimulate hair growth and to rejuvenate skin cells, but the mechanisms were not well understood, results varied, and evidence of its efficacy was largely anecdotal.

The new work is the first to document the molecular mechanism involved, thus laying the foundations for controlled treatment protocols in not only restorative dentistry but also avenues like bone regeneration and wound healing. "The scientific community is actively exploring a host of approaches to using stem cells for tissue regeneration efforts," said Wyss Institute Founding Director Don Ingber. "Dave [Mooney] and his team have added an innovative, noninvasive, and remarkably simple but powerful tool to the toolbox."

To test the team's hypothesis, Praveen Arany, an assistant clinical investigator at the National Institutes of Health, drilled holes in the molars of rats and mice, then treated them with low-dose lasers and temporary caps. Around 12 weeks later, tests confirmed that the laser treatments triggered enhanced dentin formation.

Performing dentistry on rat teeth takes extreme precision and is actually harder than the same procedure on human teeth (Image: ames Weaver, Harvard's Wyss Institute)

Further experiments were conducted on microbial cultures in the laboratory, where they found that a regulatory cell protein called transforming growth factor beta-1 (TGF-1) was activated in a chemical domino effect that in turn caused the stem cells to form dentin. The good news there is that TGF-1 is more or less ubiquitous, with key roles in many biological processes such as immune response, wound healing, development, and malignancies.

This means we could one day see the technique used to do far more than help repair teeth. But first it needs to clear planned human clinical trials, so for now you'll have to make do with dentures, canes and all manner of other prosthetics while the likes of Wolverine prance around with self-healing bodies.

A paper on the research was recently published in the journal Science Translational Medicine.

Source: Wyss Institute at Harvard

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Low-power laser triggers stem cells to repair teeth

A Harvard-led team is the first to demonstrate the ability to use low-power light to trigger stem cells inside the body to regenerate tissue, an advance they reported in Science Translational Medicine. The research, led by Wyss Institute Core Faculty member David Mooney, Ph.D., lays the foundation for a host of clinical applications in restorative dentistry and regenerative medicine more broadly, such as wound healing, bone regeneration, and more.

The team used a low-power laser to trigger human dental stem cells to form dentin, the hard tissue that is similar to bone and makes up the bulk of teeth. What's more, they outlined the precise molecular mechanism involved, and demonstrated its prowess using multiple laboratory and animal models.

A number of biologically active molecules, such as regulatory proteins called growth factors, can trigger stem cells to differentiate into different cell types. Current regeneration efforts require scientists to isolate stem cells from the body, manipulate them in a laboratory, and return them to the bodyefforts that face a host of regulatory and technical hurdles to their clinical translation. But Mooney's approach is different and, he hopes, easier to get into the hands of practicing clinicians.

"Our treatment modality does not introduce anything new to the body, and lasers are routinely used in medicine and dentistry, so the barriers to clinical translation are low," said Mooney, who is also the Robert P. Pinkas Family Professor of Bioengineering at Harvard's School of Engineering and Applied Sciences (SEAS). "It would be a substantial advance in the field if we can regenerate teeth rather than replace them."

The team first turned to lead author and dentist Praveen Arany, D.D.S., Ph.D., who is now an Assistant Clinical Investigator at the National Institutes of Health (NIH). At the time of the research, he was a Harvard graduate student and then postdoctoral fellow affiliated with SEAS and the Wyss Institute.

Arany took rodents to the laboratory version of a dentist's office to drill holes in their molars, treat the tooth pulp that contains adult dental stem cells with low-dose laser treatments, applied temporary caps, and kept the animals comfortable and healthy. After about 12 weeks, high-resolution x-ray imaging and microscopy confirmed that the laser treatments triggered the enhanced dentin formation.

"It was definitely my first time doing rodent dentistry," said Arany, who faced several technical challenges in performing oral surgery on such a small scale. The dentin was strikingly similar in composition to normal dentin, but did have slightly different morphological organization. Moreover, the typical reparative dentin bridge seen in human teeth was not as readily apparent in the minute rodent teeth, owing to the technical challenges with the procedure.

"This is one of those rare cases where it would be easier to do this work on a human," Mooney said.

Next the team performed a series of culture-based experiments to unveil the precise molecular mechanism responsible for the regenerative effects of the laser treatment. It turns out that a ubiquitous regulatory cell protein called transforming growth factor beta-1 (TGF-1) played a pivotal role in triggering the dental stem cells to grow into dentin. TGF-1 exists in latent form until activated by any number of molecules.

Here is the chemical domino effect the team confirmed: In a dose-dependent manner, the laser first induced reactive oxygen species (ROS), which are chemically active molecules containing oxygen that play an important role in cellular function. The ROS activated the latent TGF-1complex which, in turn, differentiated the stem cells into dentin.

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Researchers Use Light To Coax Stem Cells To Repair Teeth

Open wide, this won't hurt a bit. That might actually be true if the dentist's drill is replaced by a promising low-powered laser that can prompt stem cells to make damaged hard tissue in teeth grow back. Such minimally invasive treatment could one day offer an easy way to repair or regrow our pearly whites.

When a tooth is chipped or damaged, dentists replace it with ceramic or some other inert material, but these deteriorate over time.

To find something better, researchers have begun to look to regenerative medicine and in particular to stem cells to promote tissue repair. Most potential stem cell therapies require the addition of growth factors or chemicals to coax dormant stem cells to differentiate into the required cell type. These chemicals would be applied either directly to the recipient's body, or to stem cells that have been removed from the body and cultured in a dish for implantation.

But such treatments have yet to make it into the doctor's clinic because the approach needs to be precisely controlled so that the stem cells don't differentiate uncontrollably.

Praveen Arany at the National Institute of Dental and Craniofacial Research in Bethesda, Maryland, and his colleagues wondered whether they could use stem cells to heal teeth, but bypass the addition of chemicals by harnessing the body's existing mechanisms.

"Everything we need is in the existing tooth structure the adult stem cells, the growth factors, and exactly the right conditions," says Arany.

So they tried laser light, because it can promote regeneration in heart, skin, lung, and nerve tissues.

To mimic an injury, Arany's team used a drill to remove a piece of dentin the hard, calcified tissue beneath a tooth's enamel that doesn't normally regrow from the tooth of a rat. They then shone a non-ionising, low-power laser on the exposed tooth structure and the soft tissue underneath it. This allowed the light to reach the dental stem cells deep inside the pulp of the tooth.

Twelve weeks after a single 5-minute treatment, new dentin had formed in the cavity. Similar dentin production was seen in mice and in cultured human dental stem cells.

It not quite the end of the dentist's intervention though, they would still need to cap the tooth to protect it, because the stem cells that produce enamel are not present in adults.

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Forget the dentist's drill, use lasers to heal teeth

By Traci Pedersen Associate News Editor Reviewed by John M. Grohol, Psy.D. on May 25, 2014

Neurons generated from the skin cells of schizophrenia patients behave strangely in the early developmental stages, offering clues that might lead to earlier detection and treatment, according to scientists from the Salk Institute.

The study, published in the journal Molecular Psychiatry, supports the theory that the neurological dysfunction that eventually leads to schizophrenia may begin in the brains of fetuses.

This study aims to investigate the earliest detectable changes in the brain that lead to schizophrenia, said Fred H. Gage, Ph.D., professor of genetics at Salk. We were surprised at how early in the developmental process that defects in neural function could be detected.

Up until now, scientists could only study the disease by examining the brains of cadavers; but age, stress, medication, or drug abuse had often changed or damaged these brains, making it harder to figure out the where it all began.

The Salk scientists were able to go around this obstacle by using stem cell technologies. They took skin cells from patients, coaxed the cells back to an earlier stem cell form and then prompted them to grow into very early-stage neurons called neural progenitor cells (NPCs). These NPCs are similar to cells found in the brain of a fetus.

The researchers tested the cells in two ways: In one test, they looked at how far the cells moved and interacted with particular surfaces; in the other test, they looked at cell stress by imaging mitochondria, tiny organelles that generate energy for the cells.

On both tests, the NPCs from schizophrenia patients differed in significant ways from those taken from people without the disease.

In particular, cells taken from people with schizophrenia showed unusual activity in two major classes of proteins: those involved in adhesion and connectivity, and those involved in oxidative stress. Schizophrenia neural cells seemed to have aberrant migration (which may result in the poor connectivity seen later in the brain) and greater levels of oxidative stress.

These results support the current theory that eventsduring pregnancy can contribute to schizophrenia, even though symptoms typically dont begin until early adulthood. For example, previous research suggests that pregnant mothers who experience infection, malnutrition, or extreme stress are at greater risk of having children with schizophrenia.

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Skin Cell Research Suggests Schizophrenia Begins in Womb