Researchers engineer pancreatic cell transplants to evade immune responseJanuary 05, 2009Discovery moves diabetes type 1 cure closer to clinical application In a finding that could significantly influence the way type 1 diabetes is treated, researchers at Albert Einstein College of Medicine of Yeshiva University have developed a technique for transplanting insulin-producing pancreatic cells that causes only a minimal immune response in recipients. At present, cell transplantation therapy is limited because transplant recipients are forced to take powerful immunosuppressant medications that have toxic side effects and raise the risk of infection. This advance in mice, described in the online version of Gene Therapy, could pave the way for routine use of cell transplants as a therapy for type 1 diabetes in humans.
Type 1 diabetes is an incurable autoimmune disease in which the immune system mistakenly destroys the body's own pancreatic beta cells. Beta cells produce insulin, which breaks down sugar, or glucose, for use by the body. Without these cells, too much glucose builds up in the blood. High blood glucose levels damage cells and can eventually lead to complications such as heart disease, kidney disease, blindness, and premature death. Type 1 diabetes affects up to 2.4 million Americans and can develop at any age, though it typically appears during childhood or adolescence. People with type 1 diabetes must closely monitor their blood glucose levels and take daily insulin injections for life. A promising alternative to insulin injections is cellular transplantation, in which beta cells are harvested from cadavers and injected into the bloodstream of patients with diabetes; the new cells replace the recipients' destroyed pancreatic beta cells. Although such transplants can control type 1 diabetes, recipients must take immunosuppressant medications in order to prevent rejection of these beta foreign cells. "Ultimately, even with immunosuppressive therapy, most of these individuals end up rejecting the transplanted cells," says the study's principal investigator, Harris Goldstein, M.D., professor of pediatrics and of microbiology & immunology at Einstein. In this study, Dr. Goldstein and his colleagues devised a way to make foreign beta cells invisible to a transplant recipient's immune system, dramatically protecting them from rejection. They did so by harnessing the innate ability of adenoviruses to evade the body's immune surveillance system. (Adenoviruses infect tissues that line the respiratory tract, eyes, intestines, and urinary tract). After infecting cells, adenoviruses produce proteins that prevent the cells from signaling the immune system that they have been infected and should be destroyed. The viruses also produce proteins that can turn off a cell's built-in self-destruct mechanism, which is usually triggered when something disturbs a cell's internal functions. The researchers began with a special line of insulin-producing beta cells, developed at Einstein, that were harvested from mice. When injected into diabetic mice, these foreign cells can restore normal glucose control, but only temporarily. The transplanted cells are soon destroyed by the mouse's immune system and glucose levels begin to rise, returning to pre-transplant disease levels. Dr. Goldstein and his colleagues genetically engineered these beta cells to include three adenoviral genes responsible for making immunosuppressive proteins. Diabetic mice that received these engineered foreign beta cells maintained normal glucose control for up to three months. In contrast, a control group of diabetic mice that received the regular foreign beta cells exhibited normal glucose control for just a few days. "Clearly, the three proteins were not optimal, because ultimately the cells did get rejected," says Dr. Goldstein. "We are now looking at other viral genes that also contribute to immune suppression and are trying to identify the best gene combination to use." Dr. Goldstein views the current experiment as a proof of concept. "We were able to demonstrate that genetically engineered beta cells can be made highly resistant to rejection and can basically correct diabetes. This technique could conceivably be applied to protect any type of cellular transplant from rejection." However, pancreatic cell transplantation could not help treat patients with type 2 diabetes. In this form of the disease, patients have fully functional beta cells but cells throughout their body become resistant to insulin. Albert Einstein College of Medicine Science News and Science Current Events Tag Cloud This tag cloud is a visual representation of term frequencies of random science news topics with common terms grouped together and emphasized by their display size. Titanium Mortality Rate Malaria Vaccine Bone Marrow AIDS vaccine Tomato Gravitational Wave Blood Sugar Psychological Science Carbon Dioxide Gene Mutation Nanotubes Ice Shelf Evolution Pathogens Sexual Abuse Large Hadron Collider Decision Making Liver Cancer Insomnia Hygiene Emphysema Mental Disorder Heterochromatin Soybean
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Related Beta Cells Current Events and Beta Cells News Articles UT researcher: Interferon alpha can delay full onset of type I diabetes A low dose of oral interferon alpha shows promise in preserving beta cell function for patients with newly diagnosed type 1 diabetes, or juvenile diabetes. Regulating the sugar factory in diabetes Scientists in Sydney and Boston believe they may have identified a gene that controls abnormal production of sugar in the liver, a very troublesome problem for people with diabetes. Popular diabetes treatment could trigger pancreatitis, pancreatic cancer A drug widely used to treat Type 2 diabetes may have unintended effects on the pancreas that could lead to a form of low-grade pancreatitis in some patients and a greater risk of pancreatic cancer in long-term users, UCLA researchers have found. Device Protects Transplanted Pancreatic Cells from the Immune System Scientists at Burnham Institute for Medical Research (Burnham) and the University of California San Diego (UC San Diego) School of Medicine have demonstrated in mice that transplanted pancreatic precursor cells are protected from the immune system when encapsulated in polytetrafluorethylene (PTFE). New study of human pancreases links virus to cause of type 1 diabetes A team of researchers from the Peninsula Medical School in the South West of England, the University of Brighton and the Department of Pathology at Glasgow Royal Infirmary, has found that a common family of viruses (enteroviruses) may play an important role in triggering the development of diabetes, particularly in children. Assembling cells into artificial 3-D microtissues, including a tiny gland As synthetic biologists cram more and more genes into microbes to make genetically engineered organisms produce ever more complex drugs and chemicals, two University of California chemists have gone a step further. Compounds that trigger beta cell replication identified by JDRF funded researchers Researchers at the Genomics Institute of the Novartis Research Foundation (GNF) have identified a set of compounds that can trigger the proliferation of insulin-producing cells in the pancreas, using sophisticated high-throughput screening techniques. LSUHSC research may benefit diabetes by increasing understanding of how to control islet cell growth Michael Lan, PhD, Professor of Pediatrics and Genetics at LSU Health Sciences Center New Orleans, is the senior author of a paper revealing the molecular mechanism of how a protein determines the fate of the cells that make and release insulin. Stem cell research uncovers mechanism for type 2 diabetes Taking clues from their stem cell research, investigators at the University of California San Diego (UC San Diego) and Burnham Institute for Medical Research (Burnham) have discovered that a signaling pathway involved in normal pancreatic development is also associated with type 2 diabetes. Human beta cells can be easily induced to replicate, according to study in Diabetes Researchers at the University of Pittsburgh School of Medicine have successfully induced human insulin-producing cells, known as beta cells, to replicate robustly in a living animal, as well as in the lab. More Beta Cells Current Events and Beta Cells News Articles |
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