SIZE OF SHEET

Calculations to determine the sheet size needed for human implants.

Assuming:

• 500,000 islets of 150 µm diameter (see below)
• an islet-containing inner layer of 200 µm thickness

then the size of the sheet for an inner layer of solid islets is 10 cm square, a theoretical minimum.

Obviously the inner layer will not be solid islets, but will be a suspension of islets in polymer. Based on our previous experience with suspending islets in polymer gel, we believe that we will be able to form the inner layer with 1 ml of islets suspended in 2 ml of polymer. In this case, the sheet would be 17.5 cm square. We believe we might ultimately be able to suspend 1 ml of islets in 1 ml of polymer, making a sheet 14 cm square. The sheets will probably be circles or ovals with the same combined area.

Dose of lslets Needed

The number of islets needed to establish euglycemia without injected insulin in a human diabetic is important in the design of clinical trials for coated islets and is important for planning production of a commercial product. The dosage needed is not known definitively, but enough evidence exists to make an educated guess.

Injection of increasing numbers of coated islets will result in better control of the diabetic animal's blood sugar. Published reports have firmly established the relationship between numbers of islets and insulin production for autotransplants.

A human has approximately 1,000,000 islets in his pancreas. There may be considerable variation from person to person, both in islet number and total islet mass. The generally accepted conclusion is that 20% of the islets (or approximately 200,000) are sufficient to marginally restore euglycemia.

An excess of islets might be considered a potential hazard in that extra insulin causes hypoglycemia (low blood sugar). This is not the case. A healthy human has a ten-fold excess of islets, and rarely experiences hypoglycemia because islets are self regulating, and cease secreting insulin when blood sugar drops to normal levels.

The most compelling line of evidence is transplants of islets into dogs. Using autotransplantation (where rejection is not a problem), researchers have shown that in dogs 4000 to 5000 islets per kilogram are sufficient Based on the similarity in the response of humans and dogs, the islets per kilogram needed by humans should be the same as dogs.

In conclusion, approximately 4000 to 5000 islets per kilogram will be required to cure diabetes in humans. Thus a 70 kilogram (154 pound) person will require 300,000.