Plans

Phase 1 – Islet Sheet Design

The Islet Sheet has three ingredients: islets, gelled alginate, and a reinforcing mesh.  We have taken the opportunity offered by restarting to reinvestigate many aspects of sheet design and fabrication.  Although the sheets were already performing to specification, there is always room for improvement.  For example, Dr. Lakey wanted to change the handling properties of the sheets, and with a few process changes we were able make a sheets that performed surgically as requested.  We have also compared our own alginates with those from commercial suppliers and found for our purpose our alginates work best.

Another project has been to develop a small animal model for exploration of sheet fabrication.  Most of our previous work had been in large animals, an expensive model.  We have been working with the rat, which is known for sensitivity to implants, resulting in an aggressive fibrotic response.  Although we can study many more things in rats that we could in large animals it has been necessary to develop new methods for making small sheets.

We have also availed ourselves of the advanced imaging at UC Irvine.  We can now see more detailed images of the sheets in impressive detail and resolution.  In fact we can investigate certain important sheet characteristics, such as the smoothness of the surface, within minutes of making new sheets without animal implants.  We have identified some unexpected limits in our methods.

We restarted the project in July of 2008, and we expect to ‘lock in’ the final Islet Sheet design in 2009.

Phase 2 – Large animal metabolic studies

These are the studies that will tell us how well the Islet Sheet replaced islets.  Fortunately, diabetes is a well understood disease, are measurements of insulin and glucose provide a perfect surrogate for islet function.  The main difficulty in this research will be the fact that small animals such as rats have a very different insulin physiology than large animals such as pigs, dogs and monkeys.

Some of the questions the studies will answer are:

  • the best site to implant Islet Sheets
  • the dose of islets required
  • duration and type of transient anti-inflammatory treatment
  • islet function over time

We expect to start large animal studies in 2009 and determine dose and implant site by 2010.  This will permit a preclinical series to support planned clinical trials.

Phase 3 – Clinical studies

Islet Sheets with human islets will be implanted into people with type 1 diabetes.  The first few patients will probably get a low dose, with the dose rising in later patients with the goal of good blood sugars without injected insulin.

We anticipate clinical studies in 2013, perhaps sooner if research goes well and is well funded.