It has taken a very long time from the conception of a bio-artificial pancreas to the creation of the first really practical device, the Islet Sheet. The reason is, this is a very difficult thing to do.

This page is devoted to explaining our view of how to go about developing such a device. Readers with an interest in theory may wish to read this page before going on to the experiments.

Theory and Background

In this section we describe the background of our approach to developing a thin sheet bio-artificial pancreas. In an industry with a history of failure, our unique view lead us to identify the right polymer and develop methods of microencapsulation that led to prototyping of the sheet. Animal studies are underway as a precursor clinical trials.

A High-Performance Bio-Artificial Organ

Our bio-artificial endocrine pancreas replaces nonfunctioning islets of Langerhans. It responds to changing blood composition with release of hormones including insulin. Several sheets are implanted into the peritoneal cavity of the diabetic. Each sheet is several centimeters in diameter, 0.3 millimeter thick, and contains two to three million cells. Four to six sheets contain enough islet tissue to cure diabetes in an adult.

Islets are kept alive by diffusion of oxygen, glucose and other nutrients into the sheet; insulin, hormones and waste products diffuse out of the sheet. The sheet is so thin that diffusion alone allows sufficient nutrients to reach the center of the sheet. A coat on the exterior of the sheet prevents contact between the cells inside and immune effector cells of the host as well as inhibiting diffusion of antibody and complement. No immune suppression drugs are needed. The sheet may be removed or replaced at any time.

An Industry with a History of Failure

Many ventures have been founded in the past 20 years to try to profit from the opportunity for the bio-artificial pancreas. More than $200 million has been invested due to the importance of the disease, yet no product is anywhere near the marketplace, with the exception of Cerco Medical.

Our Unique View

In contrast to prior approaches, our bio-artificial pancreas is designed from the "islet's point of view" for maximum islet viability. Our approach is unique in that it has at least a theoretical chance of success it could work. For a variety of reasons, this is not true of other approaches.

Biocompatible Alginate and Microencapsulation

The first problem to be solved was a suitable polymer for the "artificial" part of the device. In the end several researchers (including Randy Dorian, a founder of ISM) concluded that the best polymer is hyper-purified alginate. This polymer is made from kelp, and has the very useful property of quickly gelling when mixed with calcium salts. Through techniques specifically developed by Cerco scientists impurities are substantially removed so that alginate is biocompatible.

We then set out to develop methods to make small microcapsules, that is, islets with a very thin, conforming coating. Success came with a combination of electrostatic micro-drop formation, overcoating with a spinning disc device, and crosslinking with fancy ion chemistry. In 1993 we implanted canine islets so coated into a diabetic dog at the University of California - Davis (click here to read more about research at the University of California). This dog remains off insulin, nearly six years later. Recently this approach was confirmed in the canine allograft model by workers at the University of California - Los Angeles supported by the current licensee of this UC microencapsulation technology, Islet Technology, Inc. This product is promising and may reach the market at about the same time as the Islet Sheet.

First Prototypes

Microencapsulated (or "coated") islets are the first generation bio-artificial pancreas. Having worked for years to make microencapsulation work, we appreciated that the ideal bio-artificial pancreas should be retrievable. We thought that a retrievable sheet would be the second-generation device. We manufactured prototype sheets and studied their properties, including strength, thickness and diffusion characteristics (click here for more.). The methods were successful, so we filed our first patent application on October 13, 1995.

Clinical Trials

Clinical studies will take place when the device is proven in diabetic animals. The FDA has already approved clinical investigation of first-generation encapsulated islets. Initial studies will be with sheets protecting allografts, that is, human islets.

Human islets in the Islet Sheet will be a profitable product but one with a market limited by the availability of human pancreases. Therefore, while human allografts are in clinical studies, research on xenografts (e.g., pig islets) and cells grown in culture will be pursued, using advanced cell culture of genetically engineered cells. These methods have the potential to produce fully functional, immunologically human islets and a lower cost than primary human islets. We are already in collaborative studies with some organizations producing such islets and cells.