Vegas also described a related line of research, testing the empty capsules of the material in the abdomen of a non-human primate. In this case, the top three alginate materials spurred a much weaker immune response than traditional materials, resulting in no scar tissue over a period of six months, even in an animal with an immune system quite similar to that of a human. Published on the same days as the Nature Medicine study, this work appeared in Nature Biotechnology<\/a>. In commenting on the two papers, an outside researcher, Cherie Stabler, an associate professor of biomedical engineering at the University of Florida said: \u201cIt\u2019s such a complex, multipronged problem that it\u2019s important to get people from different disciplines to address it. This is a great first step towards a clinically relevant, cell-based therapy for Type I diabetes.\u201d Vegas added: \u201cBeing insulin-independent is the goal. 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\u2019ve been able to develop.\u201d<\/p>\n Here\u2019s a more in-depth description of the encapsulation work, based on my visit to the lab with Vegas.<\/p>\n When Doug Melton<\/a>\u2019s Harvard lab made the announcement in October 2014 that they had succeeded in turning human stem cells into functional beta cells, Melton, in a conversation with reporters, talked, too, about the other piece of the puzzle that might enable these cells to survive T1D\u2019s autoimmune attack: encapsulation. Melton\u2019s lab is teaming up with a group of scientists in Daniel Anderson\u2019s lab at MIT\u2019s Koch Institute for Integrative Cancer Research, who for six years have been working to create alginate materials that will protect beta cells while flying under the radar screen of the body\u2019s immune system.<\/p>\n The scientist leading the work is Arturo Vegas, a chemist who started at the Koch Institute in 2008 and has led the encapsulation project since then. I sat down with Vegas for an hour or so last month, and he walked me through the work, while showing me images and videos of the materials created and tested at the lab.<\/p>\n Vegas explained that the idea of using alginate (a processed material generated from algae) to protect insulin-producing cells is not new; scientists have been testing the idea for more than thirty years. The first paper showing that you could successfully protect insulin-producing cells in an immune-competent rat came out in 1980. However, when the work was tested on primates and humans, it failed\u2014over and over again. \u201cThere have been such good results in certain models, in mice and rats, that this was a very confusing outcome in higher order animals, suddenly you were seeing this very robust foreign-body response. Once this reaction happens if you have living tissue on the inside, it\u2019s not going to survive,\u201d says Vegas.<\/p>\n In 2007, knowing about the lab\u2019s reputation for being able to solve challenges in biomedical engineering, JDRF approached two senior scientists, Daniel Anderson and Robert Langer, and asked them what they needed to take on the complicated problem of protecting beta cells through encapsulation\u2014a holy grail in type 1 diabetes research. (The project is now also funded by the Helmsley Charitable Trust; along with Melton, the lab is collaborating with Dale Greiner at UMass, Gordon Weir at Joslin, and Jose Oberholzer at the University of Illinois at Chicago; at MIT Omid Veiseh, Joshua Doloff, and Minglin Ma have made major contributions to the project too.)<\/p>\n Rather than developing a new material, Vegas decided to stick with alginate (\u201ccells love alginate,\u201d he said), but see if he could modify it so it wouldn\u2019t invite a foreign-body response. The lab, using a robotic arm funded by JDRF, made almost 800 analogues of alginate, each with a slightly different chemical structure. \u201cYou kind of have this backbone, and then you can dress it up with different things, to see if you can alter the way the immune system interacts with the material,\u201d he said. The lab then put the analogues through a series of tests, at each point winnowing the number of potential materials. The team was struck by the fact that alginate materials that had successfully encapsulated beta cells in mice in previous studies failed when tested in the MIT lab. The difference turned out to be the strain of mouse being used. The previous studies had been conducted on Balb\/c laboratory mice, whereas MIT works with B6 mice\u2014which turn out to have a more aggressive immune system, at least in terms of this type of foreign-body response. In other words, alginate materials used in these MIT mice had to get past the higher hurdle of a more robust mouse immune system. \u201cThis gave us a good entry model to start with. The other model, which was more pervasive in the literature, had been giving people a false sense of confidence in the technology,\u201d Vegas said.<\/p>\n Vegas showed me images and videos of the top ten materials, along with the commercial gold standard alginate that the lab had started with. The screen showed the different materials implanted inside the abdominal cavities of mice. In seven out of ten of them, you could see the body\u2019s immune response stained in bright colors, as macrophages (white blood cells that attack and digest foreign substances) started to cluster then buzz busily around the cells (Vegas told me that \u201cif it\u2019s a pretty picture it\u2019s a bad result). But barely any macrophages stayed near the lab\u2019s three lead materials. And those that approached bounced off the surface of the capsules. As Vegas explained it: \u201cThey aren\u2019t recognizing the material to attack. If they did, they would start attacking and get others to join the party.\u201d<\/p>\n Next he showed me images of the materials tested under more challenging circumstances: first, in the abdominal cavity of a primate, with an immune system closer to that of humans. I watched a video of a scientist trying to dislodge capsules made from the commercial gold standard alginate from a primate\u2019s abdominal cavity. In just two weeks, the primate\u2019s immune system had effectively destroyed the capsules, encasing them in a fibrous gunk, adhering them in place. But capsules made from one of the leading materials were floating freely, and could be easily removed. Even after six months the scientists could retrieve most of the latter capsules; you could just see the beginnings of an immune response to the material.<\/p>\n Second, he showed me graphics of a test using the Melton Lab\u2019s beta cells in diabetic mice. All of the images I\u2019d seen thus far had been tests of the material itself\u2014empty capsules. But cell material in the capsules spur a stronger immune attack. And human <\/em>cell material put into an immunocompetent mouse is an even greater challenge, because you\u2019re crossing the species line. Vegas showed me a graph of a diabetic mouse\u2019s blood sugar; the mouse had been implanted with Melton lab beta cells encapsulated in the commercial gold standard material; the blood sugar of the mouse was lowered for only fifteen days. Then he showed me a blood glucose graph from a mouse implanted with beta cells protected by the lab\u2019s lead material; in this case, the blood sugar was controlled for six months, the length of the experiment. This work will be described in three separate papers, which Vegas expects will be published during the coming year.<\/p>\n Anyone who follows the research knows that diabetes has been cured in mice before\u2014many times. The next step is to test the Melton Lab beta cells in primates, a process that Vegas expects will take a couple of years. Only then, and only if the encapsulation material is still a success, could the long process of human clinical trials begin.<\/p>\n For the present, a couple other methods of encapsulation are now being tested in human trials\u2014both of them macro devices, rather than micro technology like what Vegas is working on. One is ViaCyte\u2019s device<\/a> filled with stem-cell derived islet cells. Another is from Beta-O2<\/a>, now being tested on patients in Sweden, which relies on injections of oxygen into a device implanted under the skin to keep the beta cells alive.<\/p>\n As with all type 1 diabetes cure research, a solution to the particular problem of encapsulation is elusive and still years (decades?) away. But despite the long timeline and the many hurdles still to be crossed before this material could potentially be used in a clinical setting, Vegas\u2019s enthusiasm for the project is palpable. \u201cIt really is an exciting time for this research, and we are all eager to see our technology translate and improve the lives of people living with type 1 diabetes.\u201d<\/p>\n \u00a0<\/p>\n","protected":false},"excerpt":{"rendered":" \u201cThis approach has the potential to provide diabetics with a new pancreas that is protected from the immune system, which would allow them to control their blood sugar without taking drugs. That\u2019s the dream,\u201d says Daniel Anderson, an associate professor of chemical engineering at MIT, who oversaw Vegas\u2019s work.<\/p>\n","protected":false},"author":18,"featured_media":37569,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"image","meta":{"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[1446],"tags":[],"yoast_head":"\n![\"Arturo](\"https:\/\/asweetlife.org\/wp-content\/uploads\/2015\/02\/Arturo-Vegas-237x300.jpeg\")
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