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In October, a man in San Diego with type 1 diabetes had two of these thin strips implanted just under the skin of his lower back. Encapsulation is a work-around to a problem that has bedeviled researchers for more than a century: For reasons scientists haven't yet figured out, sometimes the immune system goes haywire and attacks the body's beta cells, mistaking them for dangerous invaders. For most of human history, the immune reaction that caused type 1 diabetes was a death sentence. Despite the tremendous advances made in the decades since that breakthrough, life with type 1 diabetes remains a constant challenge. For some people with type 1 diabetes, the need for insulin-producing beta cells is even more pressing.
Even before the discovery of insulin, doctors were trying to cure diabetes with transplants: In 1893, a German researcher tried putting bits of sheep pancreas in a 15-year-old boy with diabetes.
It took more than a century of research before the first successful transplantation of islets, clusters of hormone-producing cells in the pancreas that include beta cells. Though complex, the Edmonton experiments managed to succeed where so many others had failed. Finally, and most important, islet transplants don't solve the underlying cause of type 1 diabetes: an off-kilter immune system. In effect, people with type 1 diabetes must trade a long list of serious side effects, from kidney damage to increased risk of cancer, for the improved glucose control that comes with transplanted beta cells. Ever since the Edmonton researchers announced their initial results, a race has been on to find a way to keep beta cells alive without immunosuppressant drugs.
JDRF, with its focus on type 1 diabetes, has been a major supporter of research into islet and beta cell transplantation, working with scientists and industry to coordinate and support different approaches to the problem. Melton starts with stem cells, which are cells capable of transforming into any specialized cell type.
In fact, Melton says, it took 15 years of painstaking research, involving more than 50 scientists in his lab alone. Melton's announcement sparked a rush of interest in the remaining part of the puzzle: getting beta cells into the body and keeping them alive.
Though ViaCyte's Encaptra device is the first one to be tested in a human, there are lots of other people working on the problem, with product ideas that range from hockey puck–sized implants that pipe in oxygen each day to tiny beads scattered throughout the body. Microencapsulation takes the opposite approach: Each cluster of beta cells gets its own house in the suburbs.
Researchers know that making encapsulation devices an everyday reality for people with diabetes won't be easy. Kushner and his coauthors also argued that it was too early to celebrate a victory—let alone raise the hopes of people with type 1 diabetes that a cure is right around the corner.
Cornell University chemical engineer Minglin Ma, PhD, is working on new ways to "package" beta cells for encapsulation, with the help of a grant from the American Diabetes Association (ADA). Islet cells, including beta cells, make up just 2 percent of the pancreas—but use 25 percent of the oxygen that flows through the organ.
In theory, the transplanted cells could even continue growing and multiplying inside the body, causing cancers. And even if cells are shown to be safe and effective and a reliable "teabag" is developed, for the foreseeable future encapsulation will be a costly, complex procedure, requiring minor surgery to implant and a lifetime of attentive maintenance.
But to the community of scientists searching for solutions, recent developments represent a light at the end of the tunnel, no matter how distant. More than 20 years have gone by, but Melton says his kids always thought Dad would get the job done.
Register for free recipes, news you can use, and simple health tips – delivered right to your inbox. While she’s still spinning music, DJ Spinderella (aka Deidra Roper) is no longer spinning her wheels when it comes to getting the right information to help her family members who have diabetes. Since his infant son Sam was diagnosed with type 1 diabetes 23 years ago, Harvard scientist Doug Melton has dedicated his career to finding a cure for the disease.
With human embryonic stem cells as a starting point, the new cells are equivalent in most every way to normally functioning beta cells.
He hopes to be underway with human transplantation trials using the cells within a few years.
The stem cell-derived beta cells are presently undergoing trials in animal models, including non-human primates, Melton said. Many clinics that are offering stem cell treatments make claims about what stem cells can and cannot do that are not supported by our understanding of science. For millions of diabetics around the world, this is the biggest hope yet that might bring an end to daily insulin injections, the thousands of times each year they have to prick their finger with a lancet to test their blood sugar levels, or having to wear external insulin pumps while also fearing the disease’s potential long-term side effects such as blindness, kidney disease, amputations, strokes and heart attacks. In work that has just been published in the journal Cell, the Melton lab researchers have, after 15 years of trying and failing and trying and failing, have finally made a giant leap forward in diabetes research by being able to use human embryonic stem cells to produce human insulin-producing beta cells equivalent in most every way to normally-functioning beta cells.
As Professor Melton told the Harvard Gazette, “There have been previous reports of other labs deriving beta cell types from stem cells.
Jose Oberholzer, Associate Professor of Surgery, Endocrinology, and Diabetes, as well as Bioengineering, at the University of Illinois at Chicago, Director of the Islet and Pancreas Transplant Program and Chief of the Division of Transplantation, called the discovery bigger than the discovery of insulin and says the work “will leave a dent in the history of diabetes. Other funding for the research, for which Professor Melton and his colleagues are extremely grateful, came from the National Institutes of Health, The Harvard Stem Cell Institute, the JPB Foundation, and Howard and Stella Heffron.


The beginning shows a spinner flask containing red culture media and cells, the cells being too small to see. This is followed by a time-lapse series of magnified images showing how cells start off as single cells and then grow very quickly into clusters over the next few days. We’re going to turn now to health news of an advance that could eventually lead to a cure for diabetes. ROB STEIN, BYLINE: For Harvard cell biologist Doug Melton, the search for something better than insulin shots for diabetes has been a very personal quest.
STEIN: Now, Melton and his colleagues are reporting in the journal Cell that they finally found that better way.
STEIN: And when Melton and his colleagues transplanted the cells into mice with diabetes, the results were clear and fast. JOSE OLBERHOLZER: The discovery of insulin is important and certainly saved millions of people. STEIN: And so if you think about a teabag analogy, we would put ourselves inside this teabag.
DANIEL SULMASY: If, like me, someone considers the human embryo to be imbued with the same sorts of dignity that the rest of us have, then in fact this is morally problematic. NPR transcripts are created on a rush deadline by a contractor for NPR, and accuracy and availability may vary. In 2013, HSCI Co-Director Doug Melton and postdoctoral fellow Peng Yi discovered a hormone that holds promise for a dramatically more effective treatment for type 2 diabetes. HSCI Co-Director Doug Melton speaks at TEDxBeaconStreet in 2013 about the potential of stem cell biology for regenerative medicine, with a focus on finding new treatments for diseases such as diabetes. Now imagine the thin strip in your hand is fashioned out of microscopically perforated plastic and packed with hundreds of thousands of beta cells, the specialized factories that produce the insulin you need to control blood glucose levels.
It's the first time a device using beta cells grown from stem cells has been tested in a human.
Even tight blood glucose control can"t compare with the sensitivity of the body's innate insulin control system, beta cells.
Hypoglycemia unawareness, for example, keeps people from sensing low blood glucose until it's too late to fix. Researchers at the University of Edmonton in Canada successfully transplanted islets from cadavers into patients with type 1 diabetes, announcing their initial results in 2000. Patients were able to produce their own insulin and stop their regular insulin injections, at least for a time. In a paper published in the journal Cell, Melton reported that his team at Harvard managed to turn human stem cells into beta cells in a lab, consistently and in huge numbers.
They're pure potential, with the ability to transform into anything from skin cells to nerve cells to insulin-producing beta cells. Floating in a coffee cup–sized flask of reddish liquid in Melton's lab, stirred gently 70 times per minute, they might be half of the solution to the transplantation problem.
Encapsulation's goal is to offer a drug-free way to put beta cells in the body while protecting them from immune system attacks. First, the cells inside need to be hooked up to the body's plumbing system, the blood vessels that feed cells with nutrients and oxygen and transport their waste away.
In a review published in response to Melton's article in Cell, Baylor College of Medicine researcher Jake Kushner, MD, argued that the lab-grown beta cells haven't proven themselves yet. The cells don't secrete insulin in a dish nearly as well as human beta cells do in the body when stimulated by glucose (such as in response to a meal). Chris Fraker, PhD, a chemist at the University of Miami's Diabetes Research Institute, is using an ADA grant to find new materials that will help encapsulated islets get the oxygen they need.
Kushner likens the encapsulated beta cells to a scuba diver protected by a cage in shark-infested waters.
Practical questions, like how much the procedure might cost and whether insurance would cover the expense, are impossible to answer this early, JDRF spokesman Christopher Rucas says. For Melton, the research has a deeply personal element: Two of his children have type 1 diabetes. We'll check in with you twice each month to share timely tips and friendly health reminders. Today he announced that he and his colleagues have taken a giant leap forward, for the first time producing massive quantities of human insulin-producing beta cells. Melton and his colleagues have now overcome this hurdle and opened the door for drug discovery and transplantation therapy in diabetes,” Fuchs said.
Bone marrow transplant is the most widely used stem cell therapy, but some therapies derived from umbilical cord blood are also in use. When his, then, infant son Sam was diagnosed 23 years ago, Professor Melton dedicated his career to finding a cure for the disease. About 150 million beta cells are needed for transplantation into a single patient and the final pre-clinical step involves protecting those cells from the immune system by using an implantation device. Their father who also is Co-Scientific Director of the Harvard Stem Cell Institute and the University’s Department of Stem Cell and Regenerative Biology  — both of which were created more than a decade after he began his quest — said that when he told his son and daughter, they were surprisingly calm. Doug Melton has put in a lifetime of hard work in finding a way of generating human islet cells in vitro.


Pagliuca, Jeff Millman and Mads Gurtler of the Melton Lab are co-first authors on the Cell paper. If you look closely, you can see particles spinning around, the white dust or dots are clusters of cells, each containing about 1000 cells.
Before the discovery of insulin in the 1920s, diabetes was a feared disease that often led to a rapid death.
They figured out how to mass-produce the kind of cells that naturally produce insulin in the body – cells that could be transplanted into patients so their bodies could control their blood sugar normally.
This finding provides the kind of unprecedented cell source that could be used for cell transplantation therapy in diabetes.
For one thing, they need to come up with a way to hide the cells from the immune system, especially for people with Type 1 diabetes, so the immune system doesn’t attack and destroy the cell.
Some people have moral objections to anything that involves human embryonic stem cell research because it destroys human embryos. It’s the destruction of an individual unique human life for the sole purpose of helping other persons.
He’s trying to figure out if they work as well and hopes to start testing his insulin cells in people with diabetes within three years. The researchers believe that the hormone might also have a role in treating type 1, or juvenile, diabetes. ViaCyte's product is one of many different "encapsulation" devices, all essentially boxes or balls designed to keep beta cells protected and contained while letting glucose and other nutrients in and the insulin the cells make out.
When in 1922 researchers discovered how to inject insulin, the disease was transformed from terminal to chronic—manageable, but far from cured. Insulin therapy by injection or pump attempts to control the resulting blood glucose ups and downs, but is imperfect. Organ donations are hard to come by in the best cases, but donor pancreases are in particularly short supply—about 3,000 viable organs per year in the United States. Transplant recipients face a lifetime regimen of powerful and expensive immunosuppressant drugs and their potential side effects in order to keep their immune systems from ravaging the new beta cells. The first is finding a reliable, safe, and effective supply of beta cells to transplant, eliminating the need for cadaver donors.
The goal is to put transplanted clusters of beta cells and other cells, known as islets, in a flexible container with holes small enough to keep immune cells out, but large enough to let oxygen and insulin through. On the other hand, there's also the risk that the cells could produce too much background (basal) insulin, leading to uncontrolled hypoglycemia.
After his son was diagnosed with the disease as an infant, Melton devoted his career to searching for a cure. Today, insulin injections to control blood sugar levels are a mainstay of therapy for Type 1 diabetes. NPR’s Rob Stein reports on work by scientists at Harvard that could someday eliminate the need for injections. But for 15 years the researchers tried and failed and tried and failed to find just the right mix of chemical signals that would coax human embryonic stem cells into becoming insulin cells. But it’s the way you add them and the order and the timing, how long you cook it, et cetera. The finding of Doug Melton would really allow to offer them really something that I would call a functional cure, you know. No quotes from the materials contained herein may be used in any media without attribution to NPR.
Or they settle in clumps inside the abdominal cavity where they're implanted, blocking each other's access to the blood supply. Adding to the problem, he explained, is the fact that researchers can't agree on what "functionally mature" means. Anderson and his colleagues at MIT and the Koch Institute has, so far, protected beta cells implanted in mice from immune system attacks for many months while they continue to produce insulin.
They wouldn’t really feel any more being diabetic if they got a transplant of these kinds of cell. This transcript is provided for personal, noncommercial use only, pursuant to our Terms of Use. Fluctuating blood glucose levels do damage that accumulates over decades, resulting in the complications so familiar to people with diabetes: kidney, eye, and nerve problems, plus cardiovascular damage that results in an increased risk for heart attacks and strokes.
The boxier the building, the more people are stuck in the middle, hoping for a bit of sunlight.
The situation in a box full of beta cells is similar: Only the beta cells with a window have access to the blood supply.




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