Information from a leader in the field of islet cell transplantation has gotten me very excited. The novel work being done with pig islets by Encelle, Inc. appears to hold great promise for the success of cross-species islet transplantation.
Encelle, a fledgling company from Greenville, North Carolina, was co-founded by Anton-Lewis Usala, MD, a pediatric endocrinologist and associate clinical professor of pediatrics at East Carolina University. Usala has a strong background in polymer chemistry as well (his father was a polymer chemist at Dupont).
Usala, now 39 years old, has had type I diabetes since age one. He has been on multiple daily injections of insulin since the age of 10, and this gives him an even greater desire to make islet cell transplantation successful.
Using pig islets is nothing new; several others have been working with them for a few years now. But Usala and Encelle have chosen a path that seems to run counter to much of the conventional wisdom in the field. In the process, Encelle has developed Encellin XPª, an artificial pancreas that performs much like a normal pancreas.
Their approach is unique in many ways. For starters, the Encellin XP makes use of macroencapsulation. All of the transplanted islets are contained within a postage-stamp-size capsule that is transplanted between muscle layers. Most other researchers microencapsulate, or package each cell individually, and inject them into the abdomen.
The Encellin XP is also unique in the material it uses for encapsulation. The islets are suspended in a hydrogel mass which is wrapped in a thin polyester-like net. The net is then coated in a very thin layer of “stealth polymer” instead of the typical alginate coating. The polymer has no sites for proteins to bind to, so it is virtually invisible to the immune system.
These departures from the traditional paths appear to have some excellent benefits. Unlike other encapsulation techniques, Encelle does not eliminate all pancreatic tissue except islets before encapsulation. As a result, the islets are maintained in a more pancreas-like environment.
Dr. Usala encapsulates many islets together with pancreatic acinar cells (naturally occurring pancreatic material). This way, they are able to communicate and work together like the islets in a normal pancreas. Because of this storage method, Encelle claims to have kept islets alive for up to a year outside of the body.
Encelle typically takes 60 days between harvesting islets and transplanting them. Over this time they are able to test for viruses and can even detect viruses that have not yet begun to replicate. Such a test period should make these cross-species transplants even safer than human transplants. Encelle believes that this is the assurance the FDA will need to be totally comfortable with cross-species transplants.
During the 60-day storage period the capsules are refrigerated and are taken out for a “metabolic walk” once a week. On these “walks” the capsules are brought to body temperature, stimulated with glucose, and their insulin pulse response is measured. During this time they “learn” to work together in their new environment.
More importantly, however, the encapsulation technique enables the islets to release insulin more like a normal pancreas. In a person without diabetes, insulin is not secreted in a steady flow in response to rising BG levels. Instead, it is secreted in pulses, typically seven to 10 minutes apart. The secretion frequency remains fairly stable while the amount of insulin varies in response to BGs. Tissues are far more receptive to insulin’s effect when delivered in this pulsating fashion.
Because pulsed secretion results in greater sensitivity, Encelle claims to have reached normal BGs in diabetic dogs using fewer than 1,000 islets per kg of body weight compared to the minimum 10,000 islets per kg needed when using purified, individually encapsulated islets.
As I write this, Alastair Gordon, founder of The Islet Foundation in Toronto, Canada, is organizing a meeting of many of the leaders in cross-species transplantation to discuss the work being done by Usala and Encelle. “of all the initiatives in the field of (cross-species) islet transplantation, Encelle represents one of the most unique and motivated that I have encountered,” says Gordon.
If normal BGs are successfully maintained without any adverse effects in animals for a six month period, Encelle will then start human clinical trials within 12 to 18 months after the animal experiment.
If you would like to learn more about Encelle, visit The Islet Foundation web site at http://www.islet.org. While you are at the site, be sure to visit the “Public Message Forum” and post your own thoughts on the state of diabetes research today.