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March 18th, 2014
In this “reboot” series we review recent developments in encapsulated islet technology and what they mean for the future of the Islet Sheet Project. Our subject today is the oxygen problem and the company that has taken on this problem in the most direct fashion: Beta O2.
Approximately 650 million years ago the amount of oxygen in the atmosphere rose from 2% to 20%. Scientists believe that the sudden availability of massive amounts of oxygen made multicellular life possible, including large animals like us. Oxygen makes an excellent fuel because it’s rich in energy and is generally stable. But it can be dangerous, as in an out-of-control fire.
All living cells in your body require oxygen. Your blood is a red river delivering oxygen from the lungs to every other cell, tissue, and organ. Islets, like all cells, require oxygen to do their job; in their case, secreting insulin. In fact, islets require more oxygen then similar cells. It has been estimated that, although islets are only 2% of the mass of the pancreas, they account for 10% of the pancreas’s oxygen consumption.
The Islet Sheet, and all simple encapsulation devices, depend on surrounding tissues to provide oxygen to the islets inside the capsule. Computer models of oxygen diffusion and consumption indicate that oxygen levels in encapsulated islets should be sufficient for good islet function. In the real world, however, it appears that the oxygen levels actually available are lower than the models predict. This “oxygen problem” is a major element of the current crisis.
There are a number of ways to address this issue. Beta O2 has taken a direct way: generation of oxygen near the encapsulated islets.
The following figure taken from a recent publication shows how the current Beta-O2 device works.
As in the Islet Sheet, the concept is that functioning islets are protected immediately below a surface membrane. In other ways this is a more complex device, with a disk housing the islets and an oxygen-filled chamber at its center, connected by tubes to two oxygen supply ports. Oxygen from a tank is injected with a needle, through the skin and into the access ports. Thus oxygen comes from the center of the device, supplied by artificial means; the islets get other nutrients from the host.
Islet Sheet Medical has reservations about this approach. It is vulnerable to failure by the user to refill the oxygen reservoir. Conference reports suggest that a single failure to fill the oxygen bladder will result in the death of most of the encapsulated islet cells. And the paper referenced above suggests a clinical device measuring 110 x 70 mm, which seems unrealistically large. Overall it seems inelegant; there ought to be a simpler solution.
Nonetheless we applaud Beta-O2 for demonstrating the importance of the problem and a viable solution.
Next time we’ll look at other approaches to delivering oxygen to encapsulated islet systems.