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the sheet blog
The Way Things Are: Beta-O2

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.

Beta O2 device

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.

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8 Responses to “The Way Things Are: Beta-O2”

  1. Stephen Szyszkiewicz says:

    I was wondering what you guys think of the work Sernova reported on this week? they have their cell pouch but I guess they are not attempting any sort of encapsulation beyond the cell pouch itself and are depending on immunosuppressives. They seem to be having a fair amount of success, if you can believe press releases.

  2. E. S. says:

    very interesting, if they are physically injecting oxygen into the device what stops them to have a permanent way to delivering oxygen from the outside?

  3. John de Boer says:

    Hi Scott,

    I am just wondering if you will continue this series and, in particular, give an update on what has happened with the islet sheet project. From what I can tell, things haven’t gone well (particularly related to O2 absorption), but I would like to know more. I, personally, would like to know if you feel you have reached a dead end or if you are just needing to take a step back to regroup before trying again. I have been following your work since I was diagnosed 15 years ago and have appreciated how forthcoming you have been to this point. I had been hopeful you would find success. But, even if not, I appreciate the efforts of you and your team. I also hope the lessons you have learned may help others in their search for a solution.

    Anyway, I hope you are not too discouraged and we can hear more about what is happening with you and the Islet Sheet project.


  4. Scott King says:

    Hi John–

    We have put this program on indefinite hold. I’ll be posting on our reasons once I finish the post!


  5. katerinas says:

    Hi its been almost a year since the last entry on this blog. Has the Isle sheet recearch stopped?

  6. Scott King says:

    Yes, the research has ended. I will be posting our reasons when I complete the essay.

  7. Stephen Szyszkiewicz says:

    I wanted to thank you for trying.

  8. Jacob says:

    Sad to see this… I’ve been following your work, Scott, for the last five years. You answered a few questions that I had back then about alpha-antitrypsin. I hope to hear what happened, but thank you for all your efforts. This is undoubtedly a very challenging field both technically and bureaucratically.

    I think in lieu of a biological cure, focusing on intraperitoneal delivery of insulin might be the lowest hanging fruit towards achieving normalcy. Once I finish my residency (3 more years to go!), I plan on trying to get a Roche Diaport (I’ll fly to France if I have to). Insulin absorption is direct to the portal circulation, severe hypoglycemia is reduced, and patients report feeling just “better” overall. Combined with a CGM, regular exercise regimen, and a low carb diet, this might be the best we can achieve until a true biologic cure.

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