Fresh polymer coat offers diabetes hope

March 23, 2007

More than 12 million people worldwide are afflicted with Type I diabetes, an autoimmune disease in which insulin-producing pancreatic islets are damaged, thereby impeding the body’s ability to regulate glucose concentrations in the blood. One proposed therapy for this disease involves the transplantation of pancreatic islets from a donor source. The main problem with this approach is the possibility of rejection by the body’s immune system.

Now, in a major breakthrough, a collaborative team of chemists, physicists, and clinical researchers at the University of Chicag have devised a technique for coating pancreatic islets with a thin polymer shell that allows the transport of glucose and insulin but protects the islets from being attacked by the immune system.

Milan Mrksich, Sidney Nagel, Marc Garfinkel, and their colleagues have developed an encapsulation method based on the flow of water and oil through a thin tube. The islets are pulled from the water–oil interface so that they are surrounded by a uniform microscopic layer of water. In the method used by the researchers, a polymeric component present in the aqueous phase is stitched together by shining green light from a laser to start the crosslinking process. A thin and porous polymer shell is thus obtained around the islets.

“The thin coats produced by this technique may allow for more flexibility in choosing a transplantation site”, said Garfinkel, proposing that the islets could be transplanted into the portal vein that flows into the liver. The large sizes of encapsulated islets obtained by conventional methods have precluded their transplantation in these sites because of their tendency to obstruct the flow of blood in terminal blood vessels.

By controlling the thickness of the shell and the crosslinking density of the polymer, the researchers are able to exclude the smallest components of the immune system from attacking the islets, while still allowing the rapid diffusion of glucose and insulin. Remarkably, these encapsulated islets are able to match bare islets in producing insulin in response to varying concentrations of glucose.

Nagel pointed out that unlike other encapsulation methods which give a fixed outer diameter of the resulting core–shell structures, this approach enables coatings of the same thickness to be formed for islets of varying sizes. This is especially important since the islets can vary in size by a factor of five.

“The properties of the microcapsule can be systematically tuned by adding functional molecules to each polymeric layer”, added Mrksich, “for example, the outer layer can be equipped with vascular growth factors and anti-inflammatory drugs, whereas the inner layer can be modified to enhance insulin secretion”. The protection afforded to the islets from the immune system suggests that it may be possible to use islets from animal sources in replacement therapy for Type I diabetes.

Citation: Milan Mrksich, Immunoisolating Pancreatic Islets by Encapsulation with Selective Withdrawal, Small 2007, 3, No. 4, 683–690, doi: 10.1002/smll.200600231

Source: Wiley