A new study has identified an enzyme in mesenchymal stem cells (MSCs) that is responsible for creating either bone or fat a finding that scientists argue may lay the groundwork for new osteoporosis and obesity treatments.

Researchers at the Interdisciplinary Stem Cell Institute (ISCI), at the University of Miami Miller School of Medicine, say their findings are preliminary but promising.

We got very interested in the idea of there are all of these diseases of the bone that plague human beings, so we wondered if we understood the cells better, would we able to understand their role in diseases, lead study author Dr. Joshua Hare, founding director of ISCI, told FoxNews.com.

The study was conducted using mice that lacked an enzyme that regulates the level of nitric oxide signaling, a key in determining whether MSCs become fat or bone cells. MSCs from the mice that genetically lacked the enzyme made more bone cells and fewer fat cells. The researchers identified the switch, called a GSNOR, which they believe will translate clinically to help better understand how drugs may be able to manipulate the GSNOR, possibly offering future treatment for obesity and bone-disease related illnesses.

Drugs do exist to block the GSNOR. We do plan to do tests using the drug in actual circumstances of osteoporosis and study them at a very biochemical level, Hare said.

But the switch was not without consequence, as it also triggered a harmful side effect. When the animal started to produce more bone, it also turned on a pathway that created other cells to eat some of the bone, so we havent perfected the way that this would be used clinically, Hare said.

Hare said that once the potential therapy is perfected, it could have a profound effect on the aging populations quality of life.

By providing a way to produce more bone cells, MSCs create the potential to keep people active for much longer than previously possible and thus improve overall quality of life for seniors, he said.

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Study finds stem cells can be manipulated to promote bone growth

Durham, NC (PRWEB) March 31, 2015

Stem cells may provide Crohns disease sufferers relief from a common, potentially dangerous side effect fistulas according to the results of a phase 2 clinical trial published in the latest issue of STEM CELLS Translational Medicine (SCTM). After receiving an injection of their own adipose-derived stem cells (ASC), which are collected from fat tissue, the fistulas in 75 percent of the trial participants were completely healed within eight weeks of their last treatment and remained so two years later.

Crohn's disease is a painful, chronic autoimmune disorder in which the body's immune system attacks the gastrointestinal tract. Inflammation in Crohns patients can sometimes extend completely through the intestinal wall and create a fistula an abnormal connection between the intestine and another organ or skin. Left untreated, a fistula might become infected and form an abscess, which in some cases can be life threatening.

Chang Sik Yu, M.D., Ph.D., of Asan Medical Center in Seoul, Korea, a senior author of the SCTM paper, describes the results of a clinical trial conducted in collaboration with four other hospitals in South Korea, stated, Crohns fistula is one of the most distressing diseases as it decreases patients quality of life and frequently recurs. It has been reported to occur in up to 38 percent of Crohns patients and over the course of the disease, 10 to 18 percent of them must undergo a proctectomy, which is a surgical procedure to remove the rectum.

Overall, the treatments currently available for Crohns fistula remain unsatisfactory because they fail to achieve complete closure, lower recurrence and limit adverse effects, Dr. Yu said. Given the challenges and unmet medical needs in Crohns fistula, attention has turned to stem cell therapy as a possible treatment.

Several studies, including those undertaken by Dr. Yus team, suggest that mesenchymal stem cells (MSCs) do indeed improve Crohns disease and Crohns fistula. Their phase II trial involved 43 patients for a term of one year, over the period from January 2010 to August 2012. The results showed that 82 percent experienced complete closure of fistula eight weeks after the final ASC injection.

It strongly demonstrated MSCs derived from ASCs are a safe and useful therapeutic tool for the treatment of Crohns fistula, Dr. Yu said.

The latest study was intended to evaluate the long-term outcome by following 41 of the original 43 patients for yet another year. Dr. Yu reported, Our long-term follow-up found that one or two doses of autologous ASC therapy achieved complete closure of the fistulas in 75 percent of the patients at 24 months, and sustainable safety and efficacy of initial response in 83 percent. No adverse events related to ASC administration were observed. Furthermore, complete closure after initial treatment was well sustained.

These results strongly suggest that autologous ASCs may be a novel treatment option for Crohns fistulae, he said.

Stem cells derived from fat tissue are known to regulate the immune response, which may explain these successful long-term results treating Crohns fistulae with a high risk of recurrence, said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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Trial Shows Stem Cells Provide Long-Term Relief from Dangerous Crohns Side Effect

Two approaches to fat grafting -- injection of fat cells versus fat-derived stem cells -- have similar effects in reversing the cellular-level signs of aging skin, reports a study in the April issue of Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons (ASPS).

Since the facial rejuvenation results are the same, the simpler approach using fat cells plus the "stromal vascular fraction" has advantages over the more time-consuming stem cell fat technique. Dr. Gino Rigotti of Clinica San Francesco, Verona, Italy, directed a research team consisting of Luiz Charles-de-S and Natale Ferreira Gontijo-de-Amorim from Clinica Performa, Rio de Janeiro; and Andrea Sbarbati, Donatella Benati, and Paolo Bernardi from the Anatomy and Histology Institute, University of Verona.

Fat Grafts vs Stem Cells for Facial Rejuvenation

The experimental study compared the two approaches to fat grafting for regeneration of the facial skin. In these procedures, a small amount of the patient's own fat is obtained by liposuction from another part of the body, such as the abdomen. After processing, the fat is grafted (transplanted) to the treated area, such as the face.

The study included six middle-aged patients who were candidates for facelift surgery. All underwent fat grafting to a small area in front of the ear.

One group of patients received fat-derived stem cells. Isolated and grown from the patients' fat, these specialized cells have the potential to develop into several different types of tissue. The other group underwent injection of fat cells along with the stromal vascular fraction (SVF) -- a rich mix of cell types, including stem cells.

Before and three months after fat grafting, samples of skin from the treated area were obtained for in-depth examination, including electron microscopy for ultrastructural-level detail.

After injection of fat cells plus SVF, the skin samples showed reduced degeneration of the skin's elastic fiber network, or "elastosis" -- a key characteristic of aging skin. These findings were confirmed by ultrastructural examination, which demonstrated the reabsorption of the elastosis and the development of relatively "young" elastic fibers.

In patients undergoing stem cell injection, the skin changes were essentially identical. "This result seems to suggest that the effect of a fat graft is, at least in part, due to its stem cell component," Dr. Rigotti and coauthors write.

The researchers also found "suggestive" evidence that the rejuvenating effects of fat grafting are related to new formation of microscopic blood vessels. Further studies are needed to confirm this hypothesis, however. Dr. Rigotti comments, "In any case, this is the first study presenting clinical evidence showing skin rejuvenation after fat grafting and highlighting the anatomical and structural changes that are the basis of this rejuvenation."

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Two different fat graft techniques have similar effects on facial skin

Lung diseases like emphysema and pulmonary fibrosis are common among people with malfunctioning telomeres, the "caps" or ends of chromosomes. Now, researchers from Johns Hopkins say they have discovered what goes wrong and why.

Mary Armanios, M.D., an associate professor of oncology at the Johns Hopkins University School of Medicine., and her colleagues report that some stem cells vital to lung cell oxygenation undergo premature aging -- and stop dividing and proliferating -- when their telomeres are defective. The stem cells are those in the alveoli, the tiny air exchange sacs where blood takes up oxygen.

In studies of these isolated stem cells and in mice, Armanios' team discovered that dormant or senescent stem cells send out signals that recruit immune molecules to the lungs and cause the severe inflammation that is also a hallmark of emphysema and related lung diseases.

Until now, Armanios says, researchers and clinicians have thought that "inflammation alone is what drives these lung diseases and have based therapy on anti-inflammatory drugs for the last 30 years."

But the new discoveries, reported March 30 in Proceedings of the National Academy of Sciences, suggest instead that "if it's premature aging of the stem cells driving this, nothing will really get better if you don't fix that problem," Armanios says.

Acknowledging that there are no current ways to treat or replace damaged lung stem cells, Armanios says that knowing the source of the problem can redirect research efforts. "It's a new challenge that begins with the questions of whether we take on the effort to fix this defect in the cells, or try to replace the cells," she adds.

Armanios and her team say their study also found that this telomere-driven defect leaves mice extremely vulnerable to anticancer drugs like bleomycin or busulfan that are toxic to the lungs. The drugs and infectious agents like viruses kill off the cells that line the lung's air sacs. In cases of telomere dysfunction, Armanios explains, the lung stem cells can't divide and replenish these destroyed cells.

When the researchers gave these drugs to 11 mice with the lung stem cell defect, all became severely ill and died within a month.

This finding could shed light on why "sometimes people with short telomeres may have no signs of pulmonary disease whatsoever, but when they're exposed to an acute infection or to certain drugs, they develop respiratory failure," says Armanios. "We don't think anyone has ever before linked this phenomenon to stem cell failure or senescence."

In their study, the researchers genetically engineered mice to have a telomere defect that impaired the telomeres in just the lung stem cells in the alveolar epithelium, the layer of cells that lines the air sacs. "In bone marrow or other compartments, when stem cells have short telomeres, or when they age, they just die out," Armanios says. "But we found that instead, these alveolar cells just linger in the senescent stage."

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Premature aging of stem cell telomeres, not inflammation, linked to emphysema