Category Archives: Cell Medicine

The Boston Globe

Stem cell procedure could be next wave in sports medicine The Boston Globe FORT MYERS, Fla. With a painful shot in October that left him unable to bend his prized arm for days, Red Sox lefthander Drew Pomeranz joined what he and others hope is a transformative development in sports medicine. At the conclusion of the 2016 ... and more »

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Stem cell procedure could be next wave in sports medicine - The Boston Globe

Health science gets a lot of attention in the popular press. People love hearing about breakthroughs, paradigm shifts and emerging cures. The problem is, these stories are almost always misleading.

While optimistic miscalculations of the state of biomedical research may seem as if it were a harmless distraction, there is a growing body of evidence that suggests it can be the source of real social harm. It can drive unrealistic expectations, affect the public utilization of health-care resources and even shape a less-than-ideal research agenda. It can also help to legitimize the marketing of unproven therapies.

This week, the New England Journal of Medicine (NEJM) reported on three individuals who went blind after receiving an unproven stem cell treatment at a Florida clinic. The patients paid thousands of dollars for what they thought was a clinical trial on the use of stem cells to treat macular degeneration.

The primary fault, both legally and morally, for the marketing and use of unproven stem-cell therapies lies with the providers who are involved with the practice. We need national regulators (e.g., Health Canada, the U.S. Food and Drug Administration) and the bodies that oversee the relevant health-care professionals (e.g., the colleges that regulate physicians) to take a more active role a point noted by Dr. George Daley in an essay accompanying the NEJM case report.

Indeed, it is hard to blame patients for being drawn to providers that present optimistic portrayals of benefit. We live in confusing times. It is becoming increasingly difficult to tease out the real science from the bad and the fake health news from a genuinely exciting scientific advance. Not only is the science twisted by multiple systemic forces publication pressures, overenthusiastic news releases, commercial interests and media spin misinformation is being broadcast on a growing number of communication platforms. Social media, for example, have allowed for the rapid dissemination of false promises and creation of confirmation bubbles in which like-minded believers can trade anecdotes of success. And studies have shown clinics exploit platforms such as Twitter to create buzz about and demand for unproven therapies.

For the general public, here is a good rule of thumb: Doubt every claim that suggests a significant breakthrough. Doubt everything. This may sound a tad cynical, but if you adopt this approach you will be pleasantly surprised when something actually pans out. More important, this nothing-ever-works-as-promised strategy will be correct 99 per cent of the time.

For patients seeking a treatment, be cautious of any clinic offering a therapy that seems too good to be true, because virtually every time it will be too good to be true.

Consider stem-cell research. Think of all the hype, the headlines about near-future applications and the pronouncement about revolutionary regenerative therapies. This hand waving has been going on for almost two decades. So much so that the phrase stem cells has morphed into cultural marker for cutting edge. But despite all this unrelenting, upbeat noise, there are very few stem-cell therapies that are currently ready for clinical application. Daley, who is a renowned stem-cell researcher and the current dean of Harvard Medical School, concludes there are just a handful: those used for the blood-related ailments and for the skin (epithelium) conditions. The International Society for Stem Cell Research agrees with Daley and notes the list of diseases for which stem-cell treatments have been shown to be beneficial is still very short.

Dont get me wrong; I believe stem-cell research remains a fantastically promising area of science. But true medical breakthroughs are rare. Incredibly rare. In fact, if a study claims a large effect size, which is often the case in stories about breakthroughs, there is a good chance the results will be overturned by subsequent work. In a well-known 2003 analysis, it was found that out of 101 studies published between 1979 and 1983 in top science journals and framed as clinically promising interventions, only one was used extensively for the licensed indications (yes, about 99 per cent of the peer-reviewed predictions were wrong). The authors concluded that even the most promising findings of basic research take a long time to translate into clinical experimentation, and adoption in clinical practice is rare.

Yes, we need regulators to crack down on the marketing of unproven stem-cell therapies. As demonstrated by these recent reports of treatment-induced blindness, these clinics can cause serious harm. But we also need to do our best to curb the science noise that helps to legitimize the false claims made by the purveyors of stem-cell products. Scientists, clinicians, policy makers and journalists should do their best to counter misinformation in all its forms.

More good science, less science-y noise.

Timothy Caulfield is Canada Research Chair in Health Law and Policy at the University of Alberta, a Trudeau Fellow and author of Is Gwyneth Paltrow Wrong About Everything?

This story first appeared in Healthy Debate, an online publication guided by health-care professionals and patients that covers health policy and evidence-based medicine in Canada.

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Beware the hype on stem-cell breakthroughs - The Globe and Mail

To grow clusters of human stem cells that mimic organs in the lab and might be used someday in tissue implants, Bill Murphy, a UW-Madison professor of biomedical engineering, creates tiny scaffolds made of plastic or rubber.

The three-dimensional scaffolds must support the cells and feed them, help them organize and allow them to communicate.

One spring day in 2014, Murphy looked out his office window near UW Hospital, onto the universitys Lakeshore Nature Preserve, and saw a structure that does those very things naturally: plants specifically, cellulose, the main component of the cell walls of green plants.

Now, Murphy and Gianluca Fontana, a UW-Madison post-doctoral fellow with help from Olbrich Botanical Gardens have grown skin, brain, bone marrow and blood vessel cells on cellulose from plants such as parsley, spinach, vanilla and bamboo.

Plants could be an alternative to artificial scaffolds for growing stem cells, the researchers reported Monday in the journal Advanced Healthcare Materials.

Rather than having to manufacture these devices using high-tech approaches, we could literally pick them off of a tree, said Murphy, co-director of the UW-Madison Stem Cell and Regenerative Medicine Center.

The strength, porosity and large surface area of plants could prove superior to making scaffolds using current methods, such as 3-D printing and injection molding, Murphy said.

Plants have a huge capacity to grow cell populations, he said. They can deliver fluids very efficiently to their leaves ... At the microscale, theyre very well organized.

In addition, there are many plants to chose from. After Murphys inspirational gaze out the window, he and Fontana tested plants as scaffolds for stem cells using varieties they could easily obtain: parsley, spinach, jewelweed, water horsetail, summer lilac and, from the UW Arboretum, softstem bulrush.

Then Fontana asked John Wirth, Olbrich's conservatory curator, about other species that might work. Wirth invited Fontana to walk through the tropical greenhouse and take samples back to his lab.

I had never had a request like this before; it made me look at plant material in a different way, Wirth said. I think its a fantastic way of using these pieces of living tissue, to grow human tissue.

Olbrich plants that proved useful include vanilla, bamboo, wasabi, elephant ear, zebra plant and various orchids.

To use plants as scaffolds, the scientists strip away all of the cells, leaving husks of cellulose. Since human cells have no affinity for plants, they add peptides as biological fasteners.

Theyre like grappling hooks for the cells to attach to the plant, Murphy said.

To determine if plant scaffolds could really replace those made of plastic or rubber, the researchers hope to test the cellulose models in animal studies this year.

A major goal of tissue engineering is to develop implants that could regenerate tissue in people to repair bone or muscle damage after traumatic injuries, for example.

It is likely the human body wouldn't reject tissue implants formed on plant scaffolds because the plant cells would be removed, Murphy said.

Were crossing kingdoms, he said. But were optimistic that these materials would be well-tolerated.

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Borrowing from nature: UW-Madison scientists use plants to grow stem cells - Chippewa Herald

Researchers are working hard to understand the mechanism responsible for oncogenesis, the process through which normal cells become cancerous ones. A new study focuses on lactate - a molecule produced during intense exercise - and explains its role in cancer cell formation.

New research, published in the journal Carcinogenesis, analyzes the role of lactate in oncogenesis.

Lactate is a byproduct of the chemical process known as glycolysis - the breaking down of sugar, or glucose, into smaller molecules with the purpose of producing energy. During intense physical activity, lactate accumulates in the tissue and blood, which can sometimes lead to poorer physical performance and muscle stiffness.

At the beginning of the 20th century, German scientist Otto Warburg noticed that cancer cells consume a lot more glucose than normal cells. The so-called Warburg effect refers to the fact that cancer cells undergo more glycolysis and produce more lactate compared with normal cells.

The new research - led by Inigo San Millan, director of the Sports Performance Department and physiology laboratory at the University of Colorado-Boulder's Sports Medicine and Performance Center - set out to understand why the Warburg effect happens. Since Warburg's time, the focus in cancer research has shifted from cell metabolism to genetics, but the new paper hopes to put lactate back at the center of cancer research.

San Millan and colleagues suggest that the molecule is "the only metabolic compound involved and necessary" in the five stages that follow on from carcinogenesis.

The study examines the role of lactate in angiogenesis (the process by which new blood vessels form inside the tumors), immune escape (the cancer cells' ability to elude the body's immune response), and cell migration, as well as in metastasis and self-sufficient metabolism.

The paper explains how in metastasis, lactate helps to create an acidic microenvironment outside the cancer cell, which supports the spread of cancer cells.

Finally, the study also explores the link between lactate and genetic components. The researchers hypothesize that a triad of transcription factors commonly found in most cancers - HIF-1, cMYC, and p53 - also triggers and perpetuates lactate deregulation.

The crucial role of lactate in cancer cell formation may explain why people who exercise regularly are at a lower risk of developing cancer. In athletes and those who work out, the body is trained to efficiently turn lactate into an energy source for the body, thus stopping it from accumulating in excess.

Based on their findings, the researchers speculate that a sedentary lifestyle, combined with too much sugar in our diets, may lead to an excessive accumulation of lactate, thus setting the stage for cancer.

"With this paper, we open a whole new door for understanding cancer, showing for the first time that lactate is not only present, but mandatory for every step in its development."

Inigo San Millan

In the near future, San Millan will collaborate with the University of Colorado Hospital to study the effect of tailored exercise programs on cancer patients. The researcher is already studying breast cancer cell lines.

San Millan hopes that, eventually, his research will help to develop drugs that stop the lactate from accumulating. "We hope to sound the alarm for the research community that to stop cancer you have to stop lactate," he says. "There are many ways to do that," such as by targeting monocarboxylate transporters, which ferry lactate from cell to cell.

Learn how vitamin C can target and kill cancer stem cells.

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Lactate may be key for cancer development - Medical News Today

By Jamie Wells, M.D.

Dr. Jamie Wells,MD, FAAP, is a Board-Certifiedphysician with over a decade of experience caring for patients and the Director of Medicine at the American Council on Science and Health. She served as a Clinical Instructor/Attending at NYU Langone, Mt. Sinai-Beth Israel and St. Vincent's Medical Centers in Manhattan.

Dr. Wells not only graduated from Yale University with honors and was inducted as a junior and elected President of Jefferson Medical College's Alpha Omega Alpha National Medical Honor Society; but also, has been named a New York Super Doctor, repeatedly, in the NY Times magazine supplement listing the top 5% of physicians in over 30 medical specialties as chosen by their peers.

A National Merit Scholar, Dr. Wells was identified for her academic excellence early on when she also was featured as one of the top twenty high school students in the nation in USA TODAY as a recipient of their scholarship. At Yale, she was President of the Yale Science and Engineering Association, majored in American Studies and concentrated in media and film, spending her final year researching her senior essay entitled, "Ebola: The Making of an Epidemic"-- exploring the power of the governmental, political, public health and media machines and their desire to work in harmony when there is a common economic concern. In medical school, she maintained various leadership and elected positions (such as Editorials Editor of the school paper and editing guides to passing Board Exams) while creating mentoring and tutoring programs and spearheading countless volunteer activities that served the school and local Philadelphia communities.

During this time, she did research for the Department of Neurosurgery at the University of Pennsylvania School of Medicine in deep brain stimulation of the subthalamic nucleus of patients with Essential Tremor and Parkinson's Disease. She recently judged the local, district and world championships for Dean Kamens F.I.R.S.T. (For Inspiration & Recognition of Science & Technology) robotics competition and became a member of The Wistar Institute's Leadership Council (the nation's first independent biomedical research facility). She was awarded America's Top Pediatricians, Americas Top Physicians Honors of Distinction and Excellence, Compassionate Doctors Award, Patients Choice Award (honors given by patients to less than 3% of the nation's 720,000 active physicians) and been recognized for her exemplary care of those with Cystic Fibrosis. Dr. Wells was named a Doctor of Excellence which profiles the worlds leading doctors who have demonstrated success and leadership in their profession. For the better part of a decade, she answered all of the medical inquiries on line for the Boomer Esiason Cystic Fibrosis Foundation's website in a section entitled, ASK DR. WELLS.

Whether she is published, for example, in the acclaimed journal Neoreviews for a case involving a near drowning of an infant via water birth or the Huffington Post in response to the Dolce & Gabbana controversy or 10 ways to Save Your Life or the Life of a Loved One, it is a longstanding passion of hers to make science and health understanding accessible to all. She champions empowering others to be their own advocate in healthcare and has given talks to struggling expectant mothers and parenting groups, spoken on panels as well as emphasized education to patients under her care. Believing she wanted to be a brain surgeon, she began her first residency in neurosurgery, ultimately switching fields to pediatrics. As a result, her knowledge is vast in the medical realm and sought after by innumerable media outlets.

Dr. Wells greatest asset is making complicated material palatable for people in a nonthreatening, often humorous way. Her opinion as a medical expert has been showcased on live and taped local, national and international television programs that run the gamut from CNN, Fox National News Channel, ABC News, NY 1, CBS, TLC, Fox Business Network, Fox 5, Parent TV, My 9, Arise TV and so on having been featured in an hour length show on Discovery Health and, repeatedly, on Sirius Radio for Martha Stewart Living. She is a huge proponent of the health benefits of animals and was certified with her adorable and gifted English Bulldog, Mollie Joe, as an animal assist therapy team.

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Dr. Jamie Wells On Al Jazeera TV Discussing Sickle Cell Anemia ... - American Council on Science and Health

Heart inflammation, or myocarditis, is a disorder usually caused by an infection reaching the heart. Although the condition is rare, it can sometimes lead to dilated cardiomyopathy - a leading cause of heart failure in younger adults. New research helps to explain why this happens in some cases and not others, by examining an immune cell that appears to cause heart failure in mice.

Myocarditis occurs when an infection has reached the heart. During an infection, the body's immune system produces disease-fighting cells - but in heart inflammation, these cells enter the heart and can damage its muscle.

The condition is not often diagnosed; it rarely causes severe symptoms and detecting it requires a heart biopsy - a rather invasive procedure of moderate risk.

In some cases, myocarditis progresses into inflammatory dilated cardiomyopathy (DCMi) - a disorder in which the heart's muscle dilates, weakens, and can no longer properly pump blood. In the United States, DCMi is one of the leading causes of heart failure among younger adults, with a prevalence of between 300 and 400 patients per million U.S. adults.

New research, led by Dr. Daniela Cihakova from the Johns Hopkins University School of Medicine in Baltimore, MD - set out to understand why in some cases the heart heals from the inflammation, while in others it progresses into DCMi.

As the authors of the new paper mention, previous studies have pointed to the role of eosinophils - a specific type of immune cell - in the development of heart disease. As Dr. Cihakova explains, the new research "provide[s] more details about how these immune system cells may lead to deterioration of heart muscle function in mice in a way that lets us draw some parallels to human disease processes."

The findings were published in The Journal of Experimental Medicine.

Dr. Cihakova and colleagues genetically modified a group of mice to have a deficiency of eosinophils. They then induced myocarditis in this group, using a technique called experimental autoimmune myocarditis. In this procedure, mice receive a peptide from their heart muscle cells, which makes the body's immune system attack the heart.

The researchers also induced myocarditis in another group of normal mice, with a healthy level of eosinophils. After 21 days, the scientists measured the inflammation in the hearts of both groups of mice.

They also analyzed the hearts for fibrosis or scar tissue - both signs of dying heart muscles in mammals. Scar tissue is also present in cases of DCMi.

The scientists found similarly acute inflammation in both groups.

However, when the scientists examined the groups for signs of heart failure, they found drastic differences between the eosinophil-deficient group and the normal group.

The mice with normal levels of eosinophils went on to develop heart failure, whereas the mice with eosinophil deficiency displayed no signs of heart malfunction.

The team also found scar tissue in both groups to a similar degree. However, the normal mice had DCMi, while the eosinophil-deficient ones were not affected.

To see if they could replicate their findings, the team designed an additional experiment in which they genetically modified mice to have an excess of an eosinophil-producing protein called IL5.

The IL5-excessive mice developed more inflammation and more scar tissue in the heart's upper chambers (or atria) compared with normal mice.

Mice with excessive IL5 protein also had more heart-infiltrating cells. As much as 60 percent of these cells were eosinophils in the IL5-excessive mice, compared with only 3 percent in the normal mice.

Additionally, the researchers examined the mice's hearts 45 days after the experiment and found severe DCMi in the mice with too much IL5 protein.

Finally, to account for the possibility that it is the IL5 protein and not the eosinophils that drive DCMi development, the team genetically modified eosinophil-deficient mice to have an excess of the protein.

The researchers found no reduction in the heart function of these IL5-excessive, eosinophil-deficient mice, compared with normal mice. This confirms that it is the immune cells, not the protein, that causes DCMi.

In an attempt to understand exactly how eosinophils are responsible for DCMi, the researchers investigated further and managed to isolate a protein called IL4, which is produced by eosinophils.

Using yet another mouse model, Dr. Cihakova and team established that it is indeed the IL4 that facilitates the development of DCMi, and which is triggered by eosinophils.

"The take-home message is that inflammation severity does not necessarily determine long-term disease progression, but specific infiltrating cell types - eosinophils, in this case - do."

Dr. Daniela Cihakova

The study's senior author points out that their study is the first one to investigate the role of eosinophils in the onset of heart inflammation, and in its development from inflammation to DCMi.

Nicola Diny, a Ph.D. student in the Bloomberg School of Public Health and the study's first author, also comments on the findings:

"Our studies show that the presence of eosinophils in the heart makes mice more likely to get DCMi following myocarditis. And if there are a lot of eosinophils, the mice develop even more severe heart failure," Diny says. "It will be important to test if the same is true in patients. That way, we may be able to intervene early and prevent DCMi."

The researchers hope that their study will help to develop IL4-targeting medicines that could one day treat people with myocarditis, thus potentially halting its progression into DCMi.

Learn how marijuana use may temporarily weaken heart muscle.

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Immune cell may turn heart inflammation into heart failure - Medical News Today

The macula is the spot in the center of your eye's retina. When that tissue begins to thin and break down, this is referred to as macular degeneration, a blurring of the sharp central vision necessary for driving, reading and other close-up work. Most people develop this disease as they age.

For the latest study, researchers led by Dr. Michiko Mandai of the laboratory for retinal regeneration at RIKEN Center for Developmental Biology in Japan tested an experimental stem cell treatment on a 77-year-old woman diagnosed with "wet," or neovascular age-related, macular degeneration.

The "wet" form of the disease involves blood vessels positioned underneath the pigment epithelium (a layer of retinal cells) growing through the epithelium and harming the eye's photoreceptor cells. In Japan, wet age-related macular degeneration is the most common form, but in Caucasian populations, only about 10% of people with age-related macular degeneration gets that form.

The "dry" form involves the macula breaking down without growth of blood vessels where they're not supposed to be.

To stop the progress of wet macular degeneration, the researchers performed surgery to transplant a sheet of retinal pigment epithelial cells under the retina in one of the patient's eye.

The transplanted cells had been derived from autologous induced pluripotent stem cells, which are reprogrammed cells. They were created using cells from the connective tissue of the woman's skin.

One year after surgery, the transplanted sheet remained intact, and there was no evidence of lasting adverse effects. Although the patient showed no evidence of improved eyesight, her vision had stabilized.

"This research serves multiple purposes," wrote Peter Karagiannis, a science writer, in an email on behalf of Dr. Shinya Yamanaka, the Nobel Prize-winning co-author of the study and director of the Center for iPS Cell Research and Application at Kyoto University. From the patient's perspective, the study shows that induced pluripotent stem cells can alleviate the problems associated with age-related macular degeneration.

"From a greater medical perspective, however, the bigger impact is that it shows iPS cells can be used as cell therapies," the email said, adding that newly initiated stem cell research applications at the center include Parkinson's disease and thrombocytopenia, a lack of platelets in the blood.

The American story, like the Japanese story, begins with patients slowly losing their sight as a result of macular degeneration -- in this case, three women ages 72 to 88, two of whom had the "dry" form.

Each patient paid $5,000 for the procedure at an unnamed clinic in Florida, the authors noted. Some of the patients, including two of the three women described in the paper, learned of the so-called clinical trial on ClinicalTrials.gov, a registry database run by the US National Library of Medicine. However, the consent form and other written materials did not mention a trial.

The procedure took less than an hour and began with a standard blood draw and the removal of fat cells from each patient's abdomen. To obtain stem cells, the fat tissue was processed with enzymes, while platelet-dense plasma was isolated from the blood. The stem cells were mixed with the plasma and injected into both eyes.

Complications may have been caused by contamination during stem cell preparation, or the stem cells might have changed into myofibroblasts, a type of cell associated with scarring, after injection, the authors wrote.

Before the surgery, the women's vision ranged from 20/30 to 20/200. After treatment and complications, the patients were referred in June 2015 to two university-based ophthalmology practices, including the University of Miami, where lead author Dr. Ajay E. Kuriyan was practicing.

"Many stem-cell clinics are treating patients with little oversight and with no proof of efficacy," Kuriyan and his co-authors wrote in the paper, acknowledging that it is difficult for patients to know whether a stem cell therapy -- or a clinical trial -- is legitimate.

One red flag is that the patients were required to pay for their procedure; another is that both eyes were treated at once, the authors said. Legitimate clinical trials do not require payment, and for any experimental treatment of the eyes, a good doctor would observe how one eye responds before attempting the second eye.

Another problem for unsavvy patients: Listings on ClinicalTrials.gov are not fully scrutinized for scientific soundness, noted the authors.

Today, the clinic is no longer performing these eye injections, the authors said, but it is still seeing patients. In October 2015, months after the procedures had been performed, the Food and Drug Administration released more specific guidelines for stem cell treatments.

Writing on behalf of the FDA in an editorial alongside the paper, Drs. Peter W. Marks, Celia M. Witten and Robert M. Califf say there's an absence of compelling evidence, yet some practitioners argue that stem cells have a unique capacity to restore health because of their ability to differentiate into whatever cell is necessary for repairing a defect. Another argument is that clinical trials are too complex for all except large industrial sponsors.

Despite the shadow cast by some stem cell experiments, the Japanese study earned praise from the scientific community.

Michael P. Yaffe, vice president of scientific programs at the New York Stem Cell Foundation Research Institute, said the RIKEN study was "incredibly thorough, careful and well-documented."

"Many experts in the field of regenerative medicine believe that the treatment of macular degeneration and other retinal diseases will be among the first areas of success in the use of stem cell-derived tissues," said Yaffe, whose foundation was not involved in the RIKEN study.

Yaffe said this optimism stems from preliminary studies using retinal cells derived from stem cells in animals. Scientists are also hopeful because the procedures to generate pure cells of the correct type and surgical techniques necessary for transplantation have already been developed.

"A number of research groups are moving toward developing stem cell-based treatments for age-related macular degeneration and other retinal diseases," Yaffe said.

The National Eye Institute at the National Institutes of Health is planning a similar study using patient-specific pluripotent stem cells, according to Kapil Bharti, a Stadtman Investigator in the Unit on Ocular Stem Cell & Translational Research at the institute. After getting approval to conduct a phase I safety trial, the institute will treat 10 to 12 patients to check safety and tolerability of stem cell-based eye tissue transplants.

"Data from 10 to 12 patients is needed to show that the implanted cells are indeed safe," he said, adding that the trial is likely to begin in 2018.

"While researchers have used embryonic stem cell derived cells to treat age-related macular degeneration, (the RIKEN study) is the first study that used induced pluripotent stem cells," said Bharti, who was not involved in the research.

Both induced pluripotent stem cells and embryonic stem cells can be used to make other kinds of cells of the body, explained Bharti. However, induced pluripotent stem cells can be derived from adult skin or blood cells, rather than from embryos.

"Another big scientific advantage with induced pluripotent stem cells is that they can be made patient-specific (because it's the patient's own cells), reducing the chances of tissue rejection," he said.

P. Michael Iuvone, a professor of ophthalmology and director of vision research at Emory University School of Medicine, also noted the importance of using the patient's own stem cells.

Past studies have used embryonic stem cells to treat age-related macular degeneration, but there were problems related to rejection, when the body refuses to accept a transplant or graft, explained Iuvone, who was not involved in the latest study. In the new RIKEN study, the researchers took the patient's own cells and converted them into retinal cells to avoid these complications.

"The results from the standpoint of the graft taking and surviving without any signs of any kind of toxicity or tumorigenicity are very positive," Iuvone said. "But the weakness is, they only had one patient, and it's very difficult to make any conclusions from one patient."

He noted that the RIKEN researchers planned to work with more patients, but in 2014, the Japanese government passed a law that said regenerative medicine clinical trials could be performed only at medical institutions, not at research institutions such as RIKEN.

Though the experiment was performed on a woman with wet age-related macular degeneration, it also might be useful for "dry" age-related macular degeneration, which is more common in the United States, according to Iuvone.

Currently, there are some effective treatments for age-related macular degeneration.

"The standard of care in most cases is to give injections of drugs that inhibit the growth hormones that is called vascular epithelial growth factor, or VEGF," Iuvone said. "For most people, it at least slows the progression and in some cases actually improves visual acuity."

Laser treatments have also been used but are on the decrease because of side effects. "Given the fact that the VEGF treatments seem to be effective, I think that most clinicians have turned to that," Iuvone said.

Bharti believes the RIKEN study is a major milestone in the field. "We and others are learning from the Japan study," he said.

Susan L. Solomon, CEO of the New York Stem Cell Foundation Research Institute, agrees.

"This study represents a fundamental advance in regenerative medicine, in the use of stem cell-derived tissues and in the treatment of eye disease," she said. However, additional work and many more studies are needed, she said, before a safe and efficacious stem cell-based treatment will be available "to the broad and growing population with retinal disease" -- all of us, growing older.

Originally posted here:
One stem cell treatment stabilizes macular degeneration, another blinds 3 patients - CNN

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Stem Cell Therapies for Degenerative Disc Disease Clinical Pain Advisor (registration) MSC therapy offers pain relief for patients with DDD and may slow the degenerative process of this condition. ORLANDOMesenchymal stem cell (MSC) therapy, also known as regenerative medicine therapy, is emerging as a promising treatment for ...

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Stem Cell Therapies for Degenerative Disc Disease - Clinical Pain Advisor (registration)

March 17, 2017 A UT Southwestern study determined that the metabolite uridine helps the body regulate glucose. This graphic depicts how the bodys fat cell-liver-uridine axis works to maintain energy balance. Credit: UT Southwestern Medical Center

How do mammals keep two biologically crucial metabolites in balance during times when they are feeding, sleeping, and fasting? The answer may require rewriting some textbooks.

In a study published today in Science, UT Southwestern Medical Center researchers report that fat cells "have the liver's back," so to speak, to maintain tight regulation of glucose (blood sugar) and uridine, a metabolite the body uses in a range of fundamental processes such as building RNA molecules, properly making proteins, and storing glucose as energy reserves. Their study may have implications for several diseases, including diabetes, cancer, and neurological disorders.

Metabolites are substances produced by a metabolic process, such as glucose generated in the metabolism of complex sugars and starches, or amino acids used in the biosynthesis of proteins.

"Like glucose, every cell in the body needs uridine to stay alive. Glucose is needed for energy, particularly in the brain's neurons. Uridine is a basic building block for a lot of things inside the cell," said Dr. Philipp Scherer, senior author of the study and Director of UT Southwestern's Touchstone Center for Diabetes Research.

"Biology textbooks indicate that the liver produces uridine for the circulatory system," said Dr. Scherer, also Professor of Internal Medicine and Cell Biology. "But what we found is that the liver serves as the primary producer of this metabolite only in the fed state. In the fasted state, the body's fat cells take over the production of uridine."

Basically, this method of uridine production can be viewed as a division of labor. Researchers found that during fasting, the liver is busy producing glucose and so fat cells take over the role of producing uridine for the bloodstream. These findings were replicated in human, mouse, and rat studies.

Although uridine has many roles, this study is the first to report that fat cells produce plasma uridine during fasting and that a fat cell-liver-uridine axis regulates the body's energy balance.

Study lead author Dr. Yingfeng Deng, Assistant Professor of Internal Medicine, found that blood uridine levels go up during fasting and down when feeding. During feeding, the liver reduces uridine levels by secreting uridine into bile, which is transferred to the gallbladder and then sent to the gut, where it helps in the absorption of nutrients.

"It turns out that having uridine in your gut helps you absorb glucose; therefore uridine helps in glucose regulation," Dr. Scherer said.

The uridine in the blood works through the hypothalamus in the brain to affect another tightly regulated system body temperature, Dr. Scherer added. It appears that only uridine made by fat cells reduces body temperature, he said.

Among the study's other key findings:

Blood uridine levels are elevated during fasting and drop rapidly during feeding. Excess uridine is released through the bile.

The liver is the predominant uridine biosynthesis organ, contributing to blood uridine levels in the fed state.

The fat cells dominate uridine biosynthesis and blood levels in the fasted state.

The fasting-induced rise in uridine is linked to a drop in core body temperature driven by a reduction in the metabolic rate.

In dietary studies, the researchers found that prolonged exposure to a high-fat diet blunted the effects of fasting on lowering body temperature, an effect also associated with obesity. Further testing indicated those findings were due to the reduced elevation in uridine in response to fasting, said Dr. Deng, also a member of the Touchstone Diabetes Center.

Future research questions include studying the effects of feeding-induced reductions in uridine levels in organs that rely heavily on uridine from plasma, such as the heart, and whether bariatric surgery affects blood uridine levels.

"Our studies reveal a direct link between temperature regulation and metabolism, indicating that a uridine-centered model of energy balance may pave the way for future studies on uridine balance and how this process is dysregulated in the diabetic state," Dr. Scherer said.

Explore further: Size matters when it comes to keeping blood sugar levels in check

More information: Yingfeng Deng et al. An adipo-biliary-uridine axis that regulates energy homeostasis, Science (2017). DOI: 10.1126/science.aaf5375

How do mammals keep two biologically crucial metabolites in balance during times when they are feeding, sleeping, and fasting? The answer may require rewriting some textbooks.

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Fat cells step in to help liver during fasting - Medical Xpress

Guiding a recent tour of a Kyoto University lab, a staff member holds up a transparent container. Inside are tiny pale spheres, no bigger than peas, floating in a clear liquid. This is cartilage, explains the guide, Hiroyuki Wadahama. It was made here from human iPS cells.

A monitor attached to a nearby microscope shows a mass of pink and purple dots. This is the stuff from which the cartilage was grown: induced pluripotent stem cells, often called iPS cells. Scientists can create these seemingly magical cells from any cell in the body by introducing four genes, in essence turning back the cellular clock to an immature, nonspecialized state. The term pluripotent refers to the fact iPS cells can be reprogrammed to become any type of cell, from skin to liver to nerve cells. In this way they act like embryonic stem cells and share their revolutionary therapeutic potentialand as such, they could eliminate the need for using and then destroying human embryos. Also, iPS cells can proliferate infinitely.

They can also give rise, however, to potentially dangerous mutations, possibly including ones that lead to cancerous tumors. Thus, iPS cells are a double-edged swordtheir great promise is tempered by risk. Another problem is the high cost of treating a patient with his or her own newly reprogrammed cells. But now Japanese researchers are trying a different approach.

When Kyoto University researcher Shinya Yamanaka announced in 2006 that his lab had created iPS cells from mouse skin cells for the first time, biologists were stunned. In 2007, along with James Thomson of the University of WisconsinMadison, Yamanaka repeated the feat with human skin cells. Many hailed the opening of an entirely new field of personalized regenerative medicine. Need new liver cells? No problem. Patients could benefit from having their own cells reprogrammed into ones that could help treat disease, potentially eliminating the prospect of immune rejection. In 2012 Yamanaka shared the Nobel Prize in Physiology or Medicine with John Gurdon for discovering that mature cells can be converted to stem cells. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy, the Nobel judges wrote. To capitalize on the discovery, Kyoto University set up the $40-million Center for iPS Cell Research and Application (CiRA), which Yamanaka directs.

A decade after the Yamanaka teams groundbreaking discoveries, however, iPS cells have retreated from the headlines; to the layperson, progress seems scant. There has only been one clinical trial involving iPS cells, and it was halted after a transplant operation on just one patienta Japanese woman in her 70s with macular degeneration, a condition that can lead to blurry vision or partial blindness. Doctors at Kobe City Medical Center General Hospital used her skin cells to grow iPS cells, which were reprogrammed into retinal cells and implanted in her eye. The treatment stopped the degeneration but the trial was halted in 2015 because genetic mutations were detected in another batch of iPS cells intended for another patient. Regulatory changes, under which the Japanese government allowed the distribution of iPS cells for clinical use, also prompted researchers to switch the study to a more efficient process of using cells from third-party donors instead of using a patients own cells. The Japanese government has a lot of incentives to considerwere developing a new science, a new technology and also a new economic market, says CiRA spokesperson Peter Karagiannis. So theres the ethical issues, but theres also money to be made. How do we balance the two?

The Kobe clinical trial had a lot riding on it. And the setback followed a major stem cell scandal in which biologist Haruko Obokata of the Riken Center for Developmental Biology was found to have falsified data in studies, published in 2014, that claimed a new method of achieving pluripotency. Then, earlier this year, Yamanaka had to apologize at a news conference after it was discovered that a reagent used to create iPS cells at CiRA was mislabeled, which could mean the wrong reagent was used. Although the mix-up is being examined, the center has halted supplies of some of its iPS cells to researchers across Japan; the error also set back by a few years a CiRA project to produce clinical-grade platelets from iPS cells.

But Yamanaka says he remains focused on the bigger picture of iPS cells and is still optimistic they can not only help researchers but may be key to transformative clinical therapies. CiRA still has a bank of tens of millions of iPS cells that have already been reset and checked for safety, so they can be used in patient applications. In terms of regenerative medicine, things have gone quicker than I expected, Yamanaka says, adding, iPS cells have exceeded expectations because of their potential for disease modeling, which allows us to elucidate unknown disease mechanisms, and drug discovery.

Those hoping for quick clinical success should remember it takes time for revolutionary treatments to go from lab bench to bedside, says Andras Nagy, a stem cell researcher at Mount Sinai Hospitals LunenfeldTanenbaum Research Institute in Toronto, who has not been directly involved in Yamanakas work. If you fully appreciate the paradigm-shifting nature of iPS cells, tremendous progress has in fact been made over the past 10 years, says Nagy, who in 2009 established a method of creating stem cells without using viruses (which had initially been used to deliver reprogramming genes into targeted cells). By comparison, penicillin was discovered as an antibiotic in 1928, but it was not available in the clinic until the early 1940s.

Researchers in Japan are meanwhile using iPS cell technology to pave the way to better drugs. For instance, CiRAs Kohei Yamamizu recently reported developing a cellular model of the bloodbrain barrier made entirely from human iPS cells. It could become a useful tool for testing drugs for brain diseases.

All eyes, however, are back on Kobe City Medical Center General Hospital, which is resuming its retina trialthis time with iPS cells from donors instead of cells from patients themselves. Using CiRAs bank of iPS cells, there are significant time and cost savingsit could be one fifth the cost of cell preparation and patient transplant or less. The initial study, with its personalized approach, reportedly cost about $875,000 for just one patient. We plan to evaluate the efficacy of transplanting the [donor] cells and consider the feasibility of using this method as a routine treatment in the future, accessible to the wider society, study co-leader Masayo Takahashi of the RIKEN Center for Developmental Biology said at a February press conference in Kobe. Her husband Jun Takahashi, a researcher at CiRA, is also planning to use donor-derived iPS cells for a clinical applicationto help treat patients with Parkinsons disease.

Nagy admits the promise of personalized cell regeneration is probably too costly for mainstream use, and he believes genomic editingin which DNA is inserted or deletedis key to safe iPS cell implants. For his part, Yamanaka is cautiously optimistic about iPS cells as a therapeutic tool.

Regenerative medicine and drug discovery are the two key applications for iPS cells, Yamanaka says. With the use of iPS cell stock, we are now able to work quicker and cheaper, so thats the challenge going forward.

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Waiting to Reprogram Your Cells? Don't Hold Your Breath - Scientific American