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Bionic pancreas treats adults with type 1 diabetes

January 10, 2017 At a Glance A bionic pancreas system improved blood glucose control in adults with type 1 diabetes better than conventional insulin pump therapy. Larger and longer studies will be needed to further assess the benefits and risks of the automated system. The bionic pancreas system includes a continuous glucose monitor and a smart phone app that wirelessly connects with insulin and glucagon pumps. Patents for the system have been licensed to Beta Bionics. Raj Setty, Boston University Diabetes is a disorder in blood glucose levels. Glucose is a sugar that serves as fuel for the body. When blood glucose levels rise, beta cells in the pancreas normally make and secrete the hormone insulin, which triggers cells throughout the body to take up sugar from the blood. In type 1 diabetes, the body’s own immune system attacks and destroys beta cells. People with type 1 diabetes thus need to take insulin to maintain blood glucose levels within a certain range to prevent life-threatening complications. Current treatments for type 1 diabetes include carbohydrate counting, careful monitoring of blood glucose, and adjusting insulin dosing in response. A research team led by Drs. Steven J. Russell of Massachusetts General Hospital and Edward R. Damiano and Firas El-Khatib of Boston University developed and tested a bionic pancreas. The system consists of a smart phone that wirelessly communicates with 2 pumps. The pumps deliver either insulin or glucagon (a hormone that increases blood glucose levels) through tubing that goes under the skin. The hormones are administered based on readings provided to the smart phone every 5 minutes from a continuous glucose monitor. In previous short-term studies, the scientists showed that the device could maintain blood glucose levels close [...]

Diabetes missing link discovered in Auckland

05 December 2016 Professor Peter Shepherd New Zealand researchers have uncovered a new mechanism that controls the release of the hormone insulin in the body, providing hope for those with a genetic susceptibility to type 2 diabetes. The findings, published today in the Journal of Biological Chemistry, show for the first time that a protein known as beta catenin is crucial for controlling the release of insulin from the pancreas to maintain stable blood sugar levels. In type 2 diabetes, either the body doesn’t produce enough insulin or the cells in the body don’t recognise the insulin that is present, leading to high levels of glucose in the blood. University of Auckland lead researcher Professor Peter Shepherd and his team, including Dr Brie Sorrenson, carried out the study with the support of a $1.2 million project grant from the Health Research Council of New Zealand (HRC). For this part of the project they focused on a variant in a gene called TCF7L2. This variant has been known to science for about 10 years and is the biggest contributing factor for whether people are genetically susceptible to getting type 2 diabetes or not. “We wanted to understand what happens in the body’s cells that are associated with TCF7L2 and how the processes that go on affect the regulation of glucose metabolism in the body,” says Professor Shepherd. “TCF7L2 binds directly to beta catenin. By observing this interaction, we found that beta catenin levels not only change in response to rising and falling nutrient levels, but that they also regulate how much insulin we have in our body and ensure that we have the right amount of insulin at the right time.” “Scientists have built up a [...]

Researchers launch first clinical trial for Wolfram syndrome

Many people with rare genetic disease die prematurely by Jim Dryden•November 10, 2016 The drug dantrolene is a muscle relaxant approved to treat patients with cerebral palsy, multiple sclerosis and muscle spasticity. Recent research also suggests it can prevent the destruction of insulin-secreting beta cells in animal models of Wolfram syndrome. Researchers at Washington University School of Medicine in St. Louis are launching a new clinical trial to assess the safety of a drug treatment for patients with the rare disease Wolfram syndrome. Wolfram syndrome affects about one in every 500,000 people worldwide. Many of those patients die prematurely from the disease. Patients with Wolfram syndrome typically develop diabetes at a very young age and require insulin injections several times each day. The disorder also causes hearing loss, vision problems and difficulty with balance. Although doctors treat patients’ symptoms, there have not been any therapies that slow the syndrome’s progress. However, researchers at Washington University School of Medicine soon will test a drug treatment in 24 patients who have the genetic disorder. The scientists previously reported in the Proceedings of the National Academy of Sciences that the drug, dantrolene — a muscle relaxant approved to treat patients with cerebral palsy, multiple sclerosis and muscle spasticity — prevents the destruction of insulin-secreting beta cells in animal models of Wolfram syndrome and in brain cells differentiated from skin samples taken from patients with the illness. “Nobody has ever tested dantrolene in patients with Wolfram syndrome, so our first and most important objective is to make sure it’s safe,” said principal investigator Fumihiko Urano, MD, PhD, the Samuel E. Schechter Professor of Medicine. “I am very hopeful, however. The major question that I get from every patient I [...]

Innovative Regenerative Approach to Healing Diabetic Foot Ulcers Now Being Trialed at Two Additional UK sites

November 8, 2016 LONDON, UNITED KINGDOM and PERTH, AUSTRALIA and NORTHRIDGE, CA--(Marketwired - Nov 8, 2016) - Avita Medical (ASX: AVH), (OTCQX: AVMXY) Two London hospitals join the study to evaluate safety and effectiveness of new approach using ReGenerCell™ Innovative regenerative technology uses patients' own skin cells to close wounds caused by chronic Diabetic Foot Ulcers (DFUs) Diabetes costs the NHS £8.8bn pa (almost 10% of the NHS budget) with 140 diabetic patients a week having an amputation Treatment is now underway at three UK hospitals to trial an innovative approach of using a patient's own cells to close foot ulcers amongst diabetics, an affliction that leads to some 140 amputations per week across Britain. Avita Medical (ASX: AVH), (OTCQX: AVMXY), a regenerative medicine company specialized in wound treatment, said two new sites have been added to the study on the safety and effectiveness of its treatment of Diabetic Foot Ulcers (DFUs), and that ReGenerCell™ device is now deployed at London's King's College and Northwick Park Hospitals. The DFU clinical trial began earlier in 2016 at the Manchester Royal Infirmary, with seven patients already enrolled and being treated at that site. Avita said that with three sites now enlisted, enrollment can proceed apace to recruit up to 24 patients with DFUs, who will be followed over a 26-week evaluation period. Full enrollment of the trial is anticipated to be completed by early 2017. The treatment will be assessed as an adjunct to standard of care treatments, such as debridement, cleansing, dressings, and offloading. As well as the key outcome measures of incidence of healing and rate of wound closure, the study will also explore patient and physician satisfaction. ReGenerCell™, which is CE-marked and approved for sale [...]

Making Every Cell Matter

October 31, 2016 A new method for encapsulating single cells within tunable microgels could boost efficacy of cell-based therapies and tissue engineering (CAMBRIDGE, Massachusetts) – Alginate hydrogels – which are derived from the polysaccharide found in brown seaweed – have emerged as an effective material for manipulating cells and tissues due to their biocompatibility and the ability to tune their mechanical and biochemical properties to match physiological conditions found inside the body. Already they have been demonstrated to influence the differentiation of stem cells, incite immune attacks on cancer cells, and weaken tumors’ resistance to chemotherapy, but as of yet, hydrogels have mostly been useful for controlling groups of cells at large rather than individual cells. For example, alginate capsules filled with hundreds of pancreatic islet cells can be implanted in diabetic patients. However, these capsules are millimeters in size and eventually become surrounded by thick scar tissue that blocks the biological signals of islet cells and renders the implant ineffective. This image shows an encapsulated single cell rendered in three dimensions. The greenish-blue colored part in the middle is the cell nucleus; the yellow color represents the cell’s cytoskeleton; and the purple on the outside is the thin hydrogel layer that encapsulates the cell. The new microfluidic-enabled method for encapsulating single cells could pave the way for more effective cell therapies and precise tissue engineering capabilities. Credit: Wyss Institute at Harvard UniversityNow, thanks to the joint efforts of a team from the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), a new and highly effective microfluidic method for encapsulating single cells in microscale hydrogels sets the stage for a dramatic [...]

Blood-forming stem cells likely hold the key to curing many types of disease

Science Friday July 20, 2016 · 7:45 AM EDT By Adam Wernick Researchers at Stanford are reviving a technique that can use uncontaminated, blood-forming stem cells to treat a patient with cancer, autoimmune deficiency and other diseases. Beginning in the 1960s, hematopoietic, or blood-forming, stem cells became the basis for bone marrow transplants used to treat cancer patients. Then, in the 1980s and 1990s, scientists found a way to stimulate these stem cells to move from the bone marrow into the bloodstream for collection — a process called mobilization — which gradually lessened the need for bone marrow transplants. According to a 1996 study, the use of mobilized blood cells in cancer patients had multiple benefits: It led to “lower morbidity, and greater cost-effectiveness compared with conventional bone marrow transplant …and the relative ease of obtaining large amounts of stem cells made multi-cycle transplantation a viable option in the treatment of malignancies, allowing further escalation of chemotherapy dose intensity.” In 1988, Irv Weissman, a longtime stem cell researcher, developed a process that could create "purified" blood-forming stem cells from mobilized blood — that is, they could extract pure, uncomtaminated stem cells from all the other cells in the mobilized blood. This discovery became important, Weissman says, because of results found in a 1990 trial that treated women with metasticized breast cancer — cancer that has moved beyond the breast and the lymph nodes to the bones, the lung and the liver. These patients had no hope of any localized therapy to save them, but “you could give high-dose chemotherapy, and the more chemotherapy you gave the more cancer cells in the body you killed,” Weissman explains. “[But] when we looked at the mobilized blood from those women, we saw that over half of the samples [still] had breast cancer cells in [...]

WSU researchers watch skin cells ‘walk’ to wounds

JUNE 9, 2016 By Eric Sorensen, WSU science writer PULLMAN, Wash. – Skin cells typically spend their entire existence in one place on your body. But Washington State University researchers have seen how the cells will alter the proteins holding them in place and move to repair a wound. “And they walk,” said Jonathan Jones, director of WSU’s School of Molecular Biosciences and lead author of a paper on the phenomenon in the FASEB Journal. See the abstract at http://www.fasebj.org/content/early/2016/03/02/fj.201500160R.abstract. With a better understanding of the process behind the cell movement, scientists might be able to manipulate and enhance it so wounds heal more quickly. “Wound healing is deficient as we get old and also among diabetics,” said Jones. “That’s why diabetics get skin ulcers. If we could work out a way to enhance the motility of these skin cells, we could promote healing in patients that have problems with wound closure and ulceration of the skin.” Normal skin cells are typically held in place by contact with surrounding cells and proteins that bind them to underlying connective tissue. Jones and his colleagues – post-doctoral research associate Sho Hiroyasu and graduate student Zachary Colburn – saw how cells in the epidermis will dissolve the glue that binds them and reuse some of the proteins to move to seal a wound site. The cells will also grow more cells to form new, healed skin. There are pictures. Recording through a high-resolution confocal microscope that gave them the most detailed look at the process, the researchers could watch individual cells crawl – shifting from side to side to use their outer edges as “feet.” A bed of fluorescent beads let the scientists calculate the displacement forces as [...]

Stem cells from diabetic patients coaxed to become insulin-secreting cells

If damaged cells are replaceable, type 1 diabetics wouldn't need insulin shots By Jim Dryden May 10, 2016 Washington University in St. Louis, The SOURCE Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St. Louis and Harvard University have produced insulin-secreting cells from stem cells derived from patients with type 1 diabetes. People with this form of diabetes can’t make their own insulin and require regular insulin injections to control their blood sugar. The new discovery suggests a personalized treatment approach to diabetes may be on the horizon — one that relies on the patients’ own stem cells to manufacture new cells that make insulin. The researchers showed that the new cells could produce insulin when they encountered sugar. The scientists tested the cells in culture and in mice, and in both cases found that the cells secreted insulin in response to glucose. The research is published May 10 in the journal Nature Communications. “In theory, if we could replace the damaged cells in these individuals with new pancreatic beta cells — whose primary function is to store and release insulin to control blood glucose — patients with type 1 diabetes wouldn’t need insulin shots anymore,” said first author Jeffrey R. Millman, assistant professor of medicine and of biomedical engineering at Washington University School of Medicine. “The cells we’ve manufactured sense the presence of glucose and secrete insulin in response. And beta cells do a much better job controlling blood sugar than diabetic patients can.” Millman, whose laboratory is in the Division of Endocrinology, Metabolism and Lipid Research, began his research while working in the laboratory of Douglas A. Melton, Howard Hughes Medical Institute investigator and a [...]

Study Backs Pancreas Cell Transplants for Severe Diabetes

Mon, 04/18/2016 - 2:00pm By Lauran Neergaard, Associated Press Transplants of insulin-producing pancreas cells are a long hoped-for treatment for diabetes — and a new study shows they can protect the most seriously ill patients from a life-threatening complication of the disease, an important step toward U.S. approval. These transplants are used in some countries but in the U.S. they're available only through research studies. Armed with Monday's findings, researchers hope to license them for use in a small number of people with Type 1 diabetes who are most at risk for drops in blood sugar so severe they can lead to seizures, even death. "Cell-based diabetes therapy is real and works and offers tremendous potential for the right patient," said study lead author Dr. Bernhard Hering of the University of Minnesota, whose team plans to seek a Food and Drug Administration license for the therapy. In Type 1 diabetes, the immune system destroys the pancreatic cells responsible for making insulin, a hormone crucial to converting blood sugar into energy. About 1 million Americans have Type 1 diabetes and depend on regular insulin shots to survive but still can experience complications due to swings in their blood sugar. Diabetics who get kidney transplants sometimes also receive pancreas transplants at the same time, essentially curing their diabetes. But it's an uncommon and grueling operation, so scientists for years have worked on a minimally invasive alternative: Infusing patients with just islet cells, the insulin factories inside the pancreas. The questions: How best to obtain those islet cells from deceased donors, and who benefits most from transplants? When glucose levels drop too low, most people with Type 1 diabetes experience early warning signs — slurred speech, tremors, sweating, [...]

Beta cells from love handles

April 11, 2016 Researchers at ETH Zurich have managed to use a synthetic genetic program to instruct stem cells taken from fatty tissue to become cells that are almost identical to natural beta cells. This brings them a major step closer to a personal repair kit for diabetes sufferers. Researchers led by Martin Fussenegger, Professor of Biotechnology and Bioengineering at ETH Zurich's Department of Biosystems Science and Engineering in Basel, have performed a feat that many specialists had until now held to be impossible: they have extracted stem cells from a 50-year-old test subject's fatty tissue and applied genetic reprogramming to make them mature into functional beta cells. In the presence of glucose, the beta cells generated using this "genetic software" produce the hormone insulin - just like natural beta cells, which are found in the pancreas. The researchers reported this in the journal Nature Communications. Maturation dynamic reproduced The Basel-based researchers took the stem cells and added a highly complex synthetic network of genes - the genetic software. They designed this network to precisely recreate the key growth factors involved in this maturation process. Central to the process are the growth factors Ngn3, Pdx1 and MafA. Concentrations of these factors change during the differentiation process. For instance, MafA is not present at the start of maturation. Only on day four, in the final maturation step, does it appear, its concentration rising steeply and then remaining at a high level. The changes in concentration of Ngn3 and Pdx1, however, are very complex: while the concentration of Ngn3 rises and then falls again, the level of Pdx1 rises at the beginning and towards the end of maturation. Fussenegger stresses that it is essential to reproduce these [...]