In Vitro and In Vivo Studies of the Properties of an Artificial Membrane for Pancreatic Islet Encapsulation

Summary

Encapsulation of pancreatic islets with an artificial membrane has been proposed as a means of immunoprotection after transplantation. Such a membrane should be biocompatible, nondegradable, and should allow the passage of insulin and glucose while preventing that of antibodies and lymphocytes. Thus, we have studied in vitro and in vivo, the characteristics of an acrylonitrile membrane (AN69, HOSPAL, Sweden) for islet encapsulation. The AN69 membrane composed of a fiber network with a porous structure, allowed a satisfactory passage of glucose (75% of the initial amount within one hour) but not of insulin (only 7%). The morphological state of rat islets cultured on membranes under both conditions for 2 weeks was similar to that of islets cultured on dishes; in addition rat fibroblasts retracted after a 3-day culture. Finally, the membrane was unaltered after a 12 month implantation in the peritoneal cavity of rats. When the surface properties of the AN69 membrane were changed by adsorption of a hydrophilic copolymer or by protein coating, the permeability of the membrane was modified. Glucose and insulin diffusion were significantly decreased after protein-coating, whereas glucose diffusion was preserved and that of insulin doubled after adsorption of a copolymer onto the membrane. In addition, after a 12-month implantation in the rat, the membrane surface treated by the copolymer was altered leading to the adhesion of macrophages. In conclusion, the AN69 acrylonitrile membrane may be useful for pancreatic islet encapsulation; its insulin permeability should be increased by a surface treatment aimed at increasing its hydrophilic properties. However the stability of this treatment seems to be an important factor in preserving the biocompatibility of the membrane.

Key words

Islets of Langerhans - Encapsulation - Artificial Membrane - Surface Treatment - Insulin - Biocompatibility