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3D bioprinting of stem cell structures could combat osteoarthritis

Knee cartilage anatomy: the source of many problems for osteoarthritis sufferers (Image: Gray's Anatomy)

The human knee is a complex and problematic joint. I think its fair to say that it hasnt adapted well to our greatly expanded life expectancy and trend towards obesity; painful osteoarthritis is the number one cause of chronic disability in the US and many other countries.

Degradation of the knee cartilage can be brought on by all sorts of causes trauma, hereditary and developmental factors or even just plain wear and tear but the result is the same. Without healthy cartilage cushioning the point where the femur sits on top of the tibia, those two bones grind away at each other with the full weight of the body behind them, causing painful and incapacitating damage over time.

As yet, nobody has discovered a more effective barrier than human cartilage itself, so theres no shortage of research going into the creation of new cartilage to replace or repair worn out joints.

One promising stream involves the idea of using 3D printing technology to deposit stem cells directly into damaged areas of cartilage so it can grow back as healthy tissue.

Dr. Rocky Tuan, director of the Center for Cellular and Molecular Engineering at the University of Pittsburgh School of Medicine, is working on techniques that give a patients stem cells the perfect conditions to grow into healthy cartilage particularly a type of 3D bio-printed scaffolding that holds the stem cells in place to give the tissue its correct shape as it grows.

The intent is that eventually, surgeons will be able to print stable stem cell structures directly and precisely into the joint through a catheter. The technique is similar to previous attempts such as the BioPen, but with the advantage that the extruded cells are solidified using regular visible light instead of ultraviolet light, which can have a negative effect on living cells.

Dr. Tuan is now looking to improve the resilience and effectiveness of the scaffolding material using a nanofiber electrospinning technique he developed with another colleague in 2010.

Cartilage problems are debilitating, and they affect people at stages of their lives when they have maximal access to cash. Research teams are well aware of the commercial potential that can be unlocked when they find a solid solution to the problem so its fair to say that osteoarthritis is living on borrowed time. But the sword cant drop quickly enough for those of us who suffer daily joint pain.

Via 3ders.org

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3D bioprinting of stem cell structures could combat osteoarthritis

Viral 'parasites' may play a key role in the maintenance of cell pluripotency

PUBLIC RELEASE DATE:

28-Apr-2014

Contact: Jens Wilkinson gro-pr@riken.jp 81-048-462-1225 RIKEN

In a study published in Nature Genetics, scientists from the RIKEN Center for Life Science Technologies in Japan, in collaboration with the RIKEN Center for Integrative Medical Sciences, the University of Copenhagen and the Joint Genome Institute (Walnut Creek, California) have discovered that "jumping DNA" known as retrotransposonsviral elements incorporated into the human genomemay play a key role in the maintenance of pluripotency, the ability of stem cells to differentiate into many different types of body cells.

This story is part of a fundamental rethinking taking place in genomic science. In 2009, members of the FANTOM Consortium project reported that an important fraction of mammalian transcriptomesmeaning the RNA transcribed from the genomeconsists of transcripts derived from retrotransposon elements, vestiges of ancient retroviruses from the same family as HIV that have in the past been considered to only parasite the genome. However, the biological function of these "jumping DNA"associated RNA transcripts remained unknown.

In the current study on embryonic stem (ES) cells and induced pluripotent stem (iPS) cells using four high-throughput methods including cap analysis gene expression (CAGE), the researchers found that thousands of transcripts in stem cells that have not yet been annotated are transcribed from retrotransposons, presumably to elicit nuclear functions. These transcripts were found to be expressed in stem cells, but not differentiated cells. Importantly, the work showed that several of these transcripts are involved in the maintenance of pluripotency, since degrading several of them using RNA interference caused iPS cells to lose their pluripotency and differentiate.

These transcripts appear to have been recruited, surprisingly both in the human and mouse genome, where they are used to maintain the pluripotency of stem cells. Somehow, organisms including humans appear to have recruited viral elements into their genome in a way that helps to maintain the pluripotency of stem cells that allow them to regenerate. Why this is so remains a mystery for future investigation.

Although the results of the study cannot be put directly into application in regenerative medicine, knowing that retrotransposon elements are essential in the transcriptional control of iPS and ES cells is an essential clue for solving the puzzle of how to create better types of cells in future regenerative medicine studies.

"Our work has just begun to unravel the scale of unexpected functions carried out by retrotransposons and their derived transcripts in stem cell biology. We were extremely surprised to learn from our data that what was once considered genetic 'junk', namely ancient retroviruses that were thought to just parasite the genome, are in reality symbiotic elements that work closely with other genes to maintain iPS and ES cells in their undifferentiated state. This is quite different from the image given by textbooks that these genomic elements are junk," explains Dr. Piero Carninci, senior investigator of the study.

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Viral 'parasites' may play a key role in the maintenance of cell pluripotency

Recipe for Poor Wound Healing: Bacterial Infection Plus Stress

Sacramento, CA (PRWEB) April 28, 2014

The stress hormone epinephrine the source of the fight-or-flight response also heightens stresses at the cellular level, inhibiting wound healing and promoting a state of chronic inflammation that prohibits the bodys stem cells from migrating to a wound to encourage skin regeneration, UC Davis researchers have found.

The research, published in the April issue of the scientific journal Stem Cells Translational Medicine, is the first to show that epinephrine cross-activates other cellular pathways that feed off each other, generating inflammatory proteins in an exaggerated response that impedes wound healing. The research has important implications for the development of new treatments for chronic nonhealing wounds, conditions that affect more than 5 million Americans.

We have discovered that the pathways activated by the fight-or-flight hormone epinephrine and those activated by the presence of bacteria in wounds communicate with one another synergistically, greatly promoting inflammation, said Mohan R. Dasu, lead author of the study and an associate researcher in the UC Davis Department of Dermatology. The combination of stress and infection is a recipe for chronic infection.

Chronic infections are a major global health problem, with annual costs in the United States alone estimated to be more than $23 billion. Nonhealing wounds are particularly common in patients with diabetes, who often develop sores in the foot or leg that become chronic despite intensive antibiotic treatment and sometimes require amputation.

While chronic wounds are traditionally treated primarily with antibiotics, the findings open the way for enhancing therapy with agents that counteract stress hormones. Recent case studies have reported that topical treatment with beta blockers agents that block adrenergic receptors have improved chronic skin wounds, although until now, these outcomes have not been well explained.

Everyone knows that stress is harmful to the body, said Roslyn Isseroff, professor of dermatology at UC Davis and principal investigator of the study. Our findings provide a framework for systematically developing new therapeutic strategies that could selectively regulate inflammatory responses in nonhealing wounds. Isseroff is also chief of the dermatology service at the UC Davis-affiliated Department of Veterans Affairs Northern California Health Care System where she directs a multi-specialty wound clinic.

The biology of a nonhealing wound

Bacterial colonization produces in the body an inflammatory response mediated by Toll-like receptors on the cell membrane receptors that when activated, generate interleukin 6 (IL-6), a protein that plays an important role in fighting infection. Earlier work by lead author Dasu has demonstrated that activation of these receptors can contribute to nonhealing wounds in diabetic patients. In the current work, he provides an important advance to how this pathway works in the face of stress.

At the same time, wounds cause the release of stress hormones such as epinephrine that act on adrenergic receptors to also generate IL-6. Although IL-6 is essential to fighting infection, too much creates a state of chronic inflammation and actually impairs healing. Activation of adrenergic receptors also slows movement of the bodys stem cells that naturally migrate to a wound and promote healing and skin regeneration.

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Recipe for Poor Wound Healing: Bacterial Infection Plus Stress

Stem cell cloning may be aid treatment for diabetes

Scientists have moved one step closer to creating and effective diabetes treatment by creating insulin-producing cells with the DNA of a diabetic woman.

The approach could someday aid treatment of the Type 1 form of the illness, which is usually diagnosed in childhood and accounts for about 5 percent of diabetes cases in the U.S. The disease kills insulin-making cells in the pancreas. People with Type 1 diabetes use shots or a small pump to supply the hormone, which is needed to control blood sugar.

The new work is a step toward providing genetically matched replacement cells for transplant, said Dieter Egli of the New York Stem Cell Foundation Research Institute in New York. He led the research, which was reported online Monday in the journal Nature.

Doug Melton of the Harvard Stem Cell Institute, who was not involved with the work, called the paper an impressive technical achievement. But he said he believed the cells would be useful as a research tool rather than a source of transplants. They could help scientists uncover what triggers Type 1 diabetes, he said, which could in turn lead to better therapies.

Scientists had previously made insulin cells that match diabetic patients by another means, so the new work gives researchers another option for comparison. Researchers are also exploring transplants of insulin-producing cells from cadavers as a potential treatment.

The latest work used a technique that partially resembles the process used to clone animals. Basically, scientists put DNA from the woman's skin cells into donated human eggs. The eggs were grown into early embryos. From these, the scientists removed stem cells, which can grow into any cell type in the body. These stem cells were turned into the insulin-producing cells.

Egli told reporters that these cells have shown promise in animal tests, but that he could not estimate a timetable for human experiments. The new work is the third report of using the cloning approach to make human stem cells, and the first using the technique to create insulin-making cells.

Stem cells cloning is an area of research that's showing promise to treat a number of diseases. In January, Dr. Jon LaPook, chief medical correspondent for CBS News, reported an experimental stem cell treatment for patients with multiple sclerosis. Scientists have also been able to repair bones using the stem cells of fatty tissue and also use cloned cells can repair a damaged heart.

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Stem cell cloning may be aid treatment for diabetes

Stem Cell Therapies Look Promising For Heart Disease

Stem cell therapies work as a complement to standard treatments, potentially cutting the number of deaths after a year, suggests evidence from the latest Cochrane review: Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Taking stem cells from a patients bone marrow and injecting them into their damaged heart may be an effective way to treat heart disease.

The new review, published in The Cochrane Library, uses data involving 1,255 people from 23 randomised controlled trials, where all participants received standard treatments. Compared to standard treatment alone or with placebo, stem cell therapy using bone marrow cells resulted in fewer deaths due to heart disease and heart failure, reduced the likelihood of patients being readmitted to hospital, and improved heart function. However, researchers say that with much larger clinical trials underway, the findings are awaited to enable more certainty about the effects.

Dr Enca Martin-Rendon, author of the review, Cochrane Heart Review Group, and based at NHS Blood and Transplant and the University of Oxford, UK, said: This is encouraging evidence that stem cell therapy has benefits for heart disease patients. However, it is generated from small studies and it is difficult to come to any concrete conclusions until larger clinical trials that look at longer- term effects are carried out.

Stem cell therapies are experimental treatments that are currently only available in facilities carrying out medical research. If eventually found to be effective, they might offer an alternative or complementary treatment to standard drug and surgical treatments for some patients with chronic heart disease. The procedure involves collecting stem cells from a patient's own blood or bone marrow and using them to repair damaged tissues in the patient's heart and arteries.

Although within the first year there were no clear benefits of stem cell therapy over standard treatment alone, when longer term data were analysed a year or more later about 3 per cent of people treated with their stem cells had died compared with 15 per cent of people in the control groups. Hospital readmissions were reduced to 2 in every 100 people compared to 9 in the control group, and adverse effects were rare.

Dr Martin-Rendon continued, It isn't clear which types of stem cells work best or why stem cell therapies seem to work for some people but not for others. We need to find out what's different in the people who aren't responding well to these treatments as it might then be possible to tailor therapies to these patients, so that they work better."

Dr David Tovey, Editor-in-Chief, Cochrane, said: This review should help to raise awareness of the potential of stem cell therapy to improve patient outcomes, but it also demonstrates the importance of recognising the uncertainty of initial findings and the need for further research. A Cochrane review aims to analyse all available data to give a clear picture of what the evidence shows. Ensuring health decision makers, health professionals and the general public has access to up-to-date, relevant evidence research will help to raise awareness of the effectiveness of treatments and medications and therefore improve health care.

Cochrane Library

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Stem Cell Therapies Look Promising For Heart Disease

Study of stem cell trials links discrepancies in data with reported success of treatment

PUBLIC RELEASE DATE:

28-Apr-2014

Contact: Franca Davenport f.davenport@imperial.ac.uk 020-759-42198 Imperial College London

New research looking at the success of clinical trials of stem cell therapy shows that trials appear to be more successful in studies where there are more discrepancies in the trial data.

Researchers from Imperial College London conducted a meta-analysis of 49 randomised controlled trials of bone marrow stem cell therapy for heart disease. The study, published today in the British Medical Journal, identified and listed over 600 discrepancies within the trial reports.

Discrepancies were defined as two (or more) reported facts that could not both be accurate because they were logically or mathematically incompatible. For example, one trial reported that it involved 70 patients, who were divided into two groups of 35 and 80.

The researchers found eight trials that each contained over 20 discrepancies.

The researchers found that the discrepancy count in a trial was the most important determinant of the improvement in cardiac function reported by that trial. Trials with fewer and fewer discrepancies showed progressively smaller improvements in cardiac function. The five trials with no discrepancies at all showed an effect size of zero (see bar chart in Notes to Editors).

Previous meta-analyses looking at the results of lots of clinical trials have suggested that on average, bone marrow stem cell therapy has a significant positive effect on improving heart function. However, some trials have shown that it successfully improves heart function whilst others have not. The reasons for this are unclear.

Professor Darrel Francis, one of the study authors from the National Heart and Lung Institute at Imperial College London, said: "Clinical trials involve a huge amount of data and so it is understandable that discrepancies sometimes arise when researchers are presenting their findings. However, our study suggests that these discrepancies can have a significant impact on the overall results. It is a powerful reminder to all of us conducting clinical trials to be careful and vigilant to avoid discrepancies appearing in the work.

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Study of stem cell trials links discrepancies in data with reported success of treatment

Stem Cell Institute Welcomes Special Guest Speaker Roberta F. Shapiro DO, FAAPM&R to Stem Cell Therapy Public Seminar …

New York, NY (PRWEB) April 29, 2014

The Stem Cell Institute located in Panama City, Panama, welcomes special guest speaker Roberta F. Shapiro, DO, FAAPM&R to its public seminar on umbilical cord stem cell therapy on Saturday, May 17, 2014 in New York City at the New York Hilton Midtown from 1:00 pm to 4:00 pm.

Dr. Shapiro will discuss A New York Doctors Path to Panama.

Dr. Shapiro operates a private practice for physical medicine and rehabilitation in New York City. Her primary professional activities include outpatient practice focused on comprehensive treatment of acute and chronic musculoskeletal and myofascial pain syndromes using manipulation techniques, trigger point injections, tendon injections, bursae injections, nerve and motor point blocks. Secondary work at her practice focuses on the management of pediatric onset disability.

She is the founder and president of the Dayniah Fund, a non-profit charitable foundation formed to support persons with progressive debilitating diseases who are faced with catastrophic events such as surgery or illness. The Dayniah Fund educates the public about the challenges of people with disabilities and supports research on reducing the pain and suffering caused by disabling diseases and conditions.

Dr. Shapiro serves as assistant clinical professor in the Department of Rehabilitation and Regenerative Medicine at Columbia University Medical Center.

Stem Cell Institute Speakers include:

Neil Riordan PhD Clinical Trials: Umbilical Cord Mesenchymal Stem Cell Therapy for Autism and Spinal Cord Injury

Dr. Riordan is the founder of the Stem Cell Institute and Medistem Panama Inc.

Jorge Paz-Rodriguez MD Stem Cell Therapy for Autoimmune Disease: MS, Rheumatoid Arthritis and Lupus

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Stem Cell Institute Welcomes Special Guest Speaker Roberta F. Shapiro DO, FAAPM&R to Stem Cell Therapy Public Seminar ...

Researchers create artificial skin using stem cells

SAN FRANCISCO, April 28 (UPI) -- An international team of researchers developed skin grown from human stem cells that may eliminate using animals for drug and cosmetics testing and help develop news therapies for skin disorders.

The team led by Kings College London and the San Francisco Veteran Affairs Medical Center developed the first laboratory-grown epidermis -- the outer layer of skin -- similar to real skin.

"We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery."

The new skin is grown from human pluripotent stem cells -- stem cells that have the potential to differentiate into almost any cell in the body. Under the right circumstances, the stem cell can produce almost all of the cells in the body.

The human induced pluripotent stem cells can produce an unlimited supply of pure keratinocytes, the predominant cell type in the outermost layer of skin that closely match keratinocytes generated from human embryonic stem cells.

The artificial skin forms a protective barrier between the body and the environment keeping out microbes and toxins, while not allowing water from escaping the body.

The findings were published in the journal Stem Cell Reports.

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Researchers create artificial skin using stem cells