A new approach to transplanting insulin-producing islet cells offers new hope for diabetics who cannot manage their disease with regular insulin injections.
A new approach to transplanting insulin-producing islet cells offers new hope for diabetics who cannot manage their disease with regular insulin injections. The technology overcomes a key barrier to past transplants: the inability to deliver enough oxygen to islet implants. This caused the implants to fail prematurely.
About 1.25 million Americans have Type 1 diabetes, according to the American Diabetes Association. This is a chronic disease where an individual’s own immune system kills off critical insulin-producing islet cells in the pancreas, making it impossible for the body to absorb and process glucose. While most Type 1 diabetics can manage their condition with regular insulin injections, some people, called brittle diabetics, have great difficulty managing their blood glucose levels with standard treatment protocols.
Over the past two decades, many laboratories have attempted to provide relief by transplanting healthy islet cells into the pancreas. But successful transplantations remain a challenge because the immune system will attack and destroy the newly transplanted cells.
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To date, most islet cell transplantations not only require immunosuppressive drugs, but often, repeated procedures to maintain enough cells to produce the required insulin.
Clark Colton, a professor of chemical engineering at the Massachusetts Institute of Technology (MIT), argues that transplants often fail because islet cells need the right amount of oxygen not only to survive, but to produce sufficient insulin for blood sugar control. “Normally, islet cells in the pancreas are highly vascularized and receive quite a bit of oxygen-rich blood,” Colton says. “This is an issue for transplants, because if the cells don’t get enough oxygen, they won’t survive.
“But, additionally, when we’ve looked at the effect of lower oxygen on these cells in the past, we learned that as you lower the oxygen partial pressure below the levels seen in normal physiology, to less than 50 mm Hg of oxygen, you begin to decrease the rate of insulin secretion, too.”
This means that being able to appropriately oxygenate transplanted cells is key to success.
Colton, while working with Yoav Evron of Beta-O2 Technologies, an Israeli company developing new transplantation devices, wanted to come up with a new approach that could protect the transplanted islet cells from the immune system while still providing ample oxygen levels.
Building upon his own work and that of others, Colton, Evron, and colleagues developed a new device that immobilizes islet cells in a 600-micron thick slab of metal grid-reinforced alginate. On one side of the slab is a hydrophilic fluoropolymer (PTFE) membrane microporous membrane. On the other side is a silicone-PTFE membrane linked to a 5-mm-thick gas chamber that can be refilled periodically with oxygen.
This architecture protects the islets from killer immune cells but still allows oxygen and important nutrients to enter, Colton said. Critically, it also permits insulin to move out into the bloodstream.
“This device allows us to inject enriched oxygen into an internal gas chamber where it can be gradually taken up by the cells,” Colton explained. “In these first experiments, we injected the air, oxygen, with a partial pressure of about 500 mm Hg, once a day.”
Using this technique, the researchers found that 90% of the islet cells survived, even as long as eight months after transplantation, in rodent models of Type 1 diabetes. Even more importantly, the animals exhibited normal blood glucose levels while the device remained implanted.
While Colton said he and his colleagues were buoyed by the results, he believes they can develop even better devices to aid future islet cell transplantation. They are currently working on improving the device’s oxygen capacity, so it will only require weekly oxygen refills.
Beta-O2 is looking at the potential of algae and photosynthesis to help generate oxygen independently within a device, while Colton hopes to develop a wearable oxygenator that will help keep oxygen levels where they need to be.
“These improvements can allow us to keep the oxygen partial pressure more constant, and maybe even go to higher levels,” said Colton. “This would allow the device to have a higher density of cells. That means the device can be smaller, and a smaller device really is critical to patient acceptability.
“But this current approach has a lot of benefits: The islets stay alive, the islets produce the required insulin, and you are less likely to provoke an immune response.”
Kayt Sukel is an independent technology writer.
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