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Breakthrough Research on Encapsulated pancreatic cells offer possible new diabetes treatment.

Reporter: Eveline B. Cohn, PhD

It is known that in patients with Type 1 diabetes the immune system attacks the pancreas, and the monitoring of blood sugar becomes really difficult. Lately the research showed a possibility of replacing the pancreatic islets cells with healthy cells to take over glucose monitoring and insulin release. However the immune system attacked the transplanted cells, patients being obliged to take immunosuppressant drugs for the rest of their life.
Now , a new advance in this type of research by Boston Children’s Hospital designed a material that was used to encapsulate human islet before transplanted them. In animal testing it was showed that the encapsulated human cells could cure diabetes for up to six months without provoking an immune response.
This approach “has the potential to provide diabetics with a new pancreas that is protected from the immune system, which allow them to control their blood sugar without taking drugs. That’s the dream” says Daniel Anderson, The Samuel A Goldblith Associate Professor in MIT’s Department of Chemical Engineering, A member of MIT’s Koch Institute for integrative Cancer research and Institute for Medical Engineering and Science (IMES), and a research fellow in the department of Anesthesiology at Boston Children’s Hospital
The JDRF director Julia Greenstein, Anderson, Langer and colleagues explored a chemical derivative originally isolated from brown algae to encapsulate the cells without harming them, allowing sugar and proteins to go through, thus permitted to test the glucose level after transplantation of the encapsulated cells. The research was published in Nature Medicine and Nature Biotechnology. Researchers from Harvard University, University of Illinois at Chicago and Joslin Diabetes Center and University of Massachusetts Medical school also contributed to this research.
Previous research has shown that when alginate capsules are implanted in primates and humans, scar tissue builds up around the capsules, making the device ineffective. MIT/Children Hospital try to modify alginate make it less likely to provoke this kind of immune response.

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“We decided to take an approach where you cast a very wide net and see what you can catch,” says Arturo Vegas, a former MIT and Boston Children’s Hospital postdoc who is now an assistant professor at Boston University. Vegas is the first author of the Nature Biotechnology paper and co-first author of the Nature Medicine paper. “We made all these derivatives of alginate by attaching different small molecules to the polymer chain, in hopes that these small molecule modifications would somehow give it the ability to prevent recognition by the immune system.”
800 alginate derivatives were screened . Further, the known triazole thiomorpholine dioxide (TMTD) have been chosen to be tested in diabetic mice. They chose a strain of mice with a strong immune system and implanted human islet cells encapsulated in TMTD into a region of the abdominal cavity known as the intraperitoneal space.
The pancreatic islet cells used in this study were generated from human stem cells using a technique recently developed by Douglas Melton, a professor at Harvard University who is an author of the Nature Medicine paper.
Following implantation, the cells immediately began producing insulin in response to blood sugar levels and were able to keep blood sugar under control for the length of the study, 174 days.
“The really exciting part of this was being able to show, in an immune-competent mouse, that when encapsulated these cells do survive for a long period of time, at least six months,” says Omid Veiseh, a senior postdoc at the Koch Institute and Boston Children’s hospital, co-first author of the Nature Medicine paper, and an author of the Nature Biotechnology paper. “The cells can sense glucose and secrete insulin in a controlled manner, alleviating the mice’s need for injected insulin.”
The researchers also found that 1.5-millimeter diameter capsules made from their best materials (but not carrying islet cells) could be implanted into the intraperitoneal space of nonhuman primates for at least six months without scar tissue building up.
“The combined results from these two papers suggests that these capsules have real potential to protect transplanted cells in human patients,” says Robert Langer, the David H. Koch Institute Professor at MIT, a senior research associate at Boston’s Children Hospital, and co-author on both papers. “We are so pleased to see this research in cell transplantation reach these important milestones.”
Cherie Stabler, an associate professor of biomedical engineering at the University of Florida, says this approach is impressive because it tackles all aspects of the problem of islet cell delivery, including finding a source of cells, preventing an immune response, and developing a suitable delivery material.
“It’s such a complex, multipronged problem that it’s important to get people from different disciplines to address it,” says Stabler, who was not involved in the research. “This is a great first step towards a clinically relevant, cell-based therapy for Type I diabetes.”

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https://www.youtube.com/watch?v=cw3EbB8DAq8

At this point the researchers are thinking of using their new material in non human primates and eventually performing clinical trials in diabetic patients. “Our goal is to continue to work hard to translate these promising results into a therapy that can help people,” Anderson says.
“Being insulin-independent is the goal,” Vegas says. “This would be a state-of-the-art way of doing that, better than any other technology could. Cells are able to detect glucose and release insulin far better than any piece of technology we’ve been able to develop.”
In their research they found out that the new material works best with molecules containing triazole group- a ring containing two atoms of Carbon and three of N. However, they suspect that in this particular case it may interfere with the immune system’s ability to recognize the material as foreign.

The work was supported, in part, by the JDRF, the Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health, and the Tayebati Family Foundation.
Other authors of the papers include MIT postdoc Joshua Doloff; former MIT postdocs Minglin Ma and Kaitlin Bratlie; MIT graduate students Hok Hei Tam and Andrew Bader; Jeffrey Millman, an associate professor at Washington University School of Medicine; Mads Gürtler, a former Harvard graduate student; Matt Bochenek, a graduate student at the University of Illinois at Chicago; Dale Greiner, a professor of medicine at the University of Massachusetts Medical School; Jose Oberholzer, an associate professor at the University of Illinois at Chicago; and Gordon Weir, a professor of medicine at the Joslin Diabetes Center.

SOURCE

http://news.mit.edu/2016/pancreatic-cells-diabetes-treatment-insulin-injections-0125?elq=6d9b90a822f04183bd0b059d36eb2b7a&elqCampaignId=9&elqaid=14548&elqat=1&elqTrackId=d91b7d01a9d14b199e41b4deb2c10ac6