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Encelle - A Novel Approach...

In any field of research, progress occurs in many different ways. In pursuing islet xenotransplantation as a cure for diabetes, each research team applies and tests certain unique principals and practices. As the world learns which approaches work and which do not, our knowledge grows and we get closer to our goal. Without such diversity, we cannot have trial and error, the basis for all human progress. One company, with a highly motivated founder and superb team of scientists and engineers, offers an approach to our mission which stands apart from the mainstream.

Encelle, Inc., a young company in Greenville, North Carolina, is a fascinating new entry in the world of encapsulated islet xenotransplantation. They appear to be at odds with all the conventional wisdom in the field today, and actual results are preliminary. However, their approach produces a bioartificial pancreas - Encellin XP - that is much closer to the environment and behavior of a normal pancreas.

The founder is Dr. Anton-Lewis Usala, a Pediatric Endocrinologist and Clinical Associate Professor of Pediatrics at East Carolina University, with a strong background in polymer chemistry (His father was a polymer chemist at Dupont, and an inventor of Lucite). Perhaps the most compelling aspect of Encelle is that Dr. Usala has had type 1 diabetes since age one, and at 40 years of age, has non-diabetic glycated hemoglobin values, no retinopathy, and is in good health (using multiple daily injections of insulin since age 10). The source of his motivation is self-evident.

The following is a list of all the things that Encelle is doing differently from current conventional wisdom in the field of islet xenotransplantation, and the benefits which the company claims:

• Encellin XP uses macroencapsulation, not microencapsulation. All the islets are contained within a postage-stamp-sized device.
• The capsule is transplanted intramuscularly (typically the shoulder muscle), not in the peritoneal cavity. Dr. Usala claims better results because of superior vascularization and higher oxygen tension. If necessary, complete retrieval is simple and assured.
• The protective layer is a stealth polymer, not alginate. This polymer provides no sites for the binding of proteins, and is therefore invisible to the immune system. Encelle has found no fibrosis following implantation in dogs, rats, and mice for up to a year.
• The capsule consists of pig islets trapped in a hydrogel matrix which is wrapped in a thin polyester net which is then coated in a very thin (about 1,000 angstroms) coating of the stealth polymer.
• The hydrogel is solid at room temperature, liquid at body temperature. During the application of the stealth polymer, the hydrogel is solid and protects the islets from damage. Once implanted in the body, the hydrogel becomes a liquid and allows rapid transit of glucose and insulin, thereby facilitating a pancreas-like response time to blood glucose changes.
• Encelle deliberately avoids purification of the islets, whereas others aim for very high purity in order to assure that no acinar tissue remains. The islets are maintained in a much more pancreas-like environment than individual microencapsulated islets.
• The Encelle capsule maintains the pulsatility of insulin secretion found in the pancreas. In other words, islets in a normal pancreas do not simply increase a steady flow of insulin in response to rising blood glucose levels. Instead, the secretion from the islets is coordinated to produce pulses of insulin, typically 7 to 10 minutes apart. The amplitude of these pulses increases in response to rising glucose, but the frequency is relatively stable. When insulin is secreted in pulses, tissue receptors are much more sensitive to its effect. Microencapsulated islets without acinar are unable to communicate with each other and synchronize their secretion pulses. However, by retaining the acinar, the Encellin XP capsule maintains pulsatility in its insulin secretion, and hence may be more effective at glucose control than a continuously modulated insulin secretion.
• Encelle claims to be able to reach euglycemia (normal blood glucose with no injected insulin) with fewer than 1,000 islets per kg of body weight, versus at least 10,000 islets per kg for pure islets. This startling difference is attributed to the higher insulin sensitivity resulting from the pulsatility.
• Encelle claims that their capsule creates an embryonic environment for the islets and acinar tissue. As a result, there may be some limited replication of islets which continues for about 60 days. They prefer to wait for this replication and recovery period before completing the transplant.
• During the storage period, the capsules are stored in a refrigerator and taken for a weekly "metabolic walk" in which they are removed from the fridge, allowed to return to body temperature, stimulated with glucose, and measured for insulin pulse response. They have kept islets alive for up to a year in vitro using this method. No cryogenic storage is required.
• Encelle does not need Specific Pathogen Free (SPF) pigs. They are unique in that the time between harvesting the islets and transplanting the patient is typically 60 days, whereas other methods require immediate transplantation. During this period they can culture samples and test extensively for viruses, and can even use Polymerase Chain Reaction (PCR) to detect viruses that have not begun replicating..
• In the Encellin XP capsule, the islets tend to migrate to the wall of the capsule during the 60-day storage period, and therefore arrange themselves for maximum contact with the blood when transplanted. Some other attempts at macroencapsulation have resulted in the early death of islets which are distant from the capsule wall, and hence from the blood supply.
• Encelle has had success in depancreatized dogs showing responsive insulin production and no fibrosis for up to 4 months.

Read about the visit to Encelle on May 15/16 by a scientific and charitable delegation
 Raleigh News & Observer - Dec 23 1998 - Encelle testing diabetes remedy
 Diabetes Mall - Dec 26, 1998 - Encelle Receives Research Funding For Beta Cell Transplants
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