Control of complement activities for immunoisolation.

Immunoisolation of cells by semipermeable membranes is a most promising approach to transplant xenogeneic cells. Although membranes which allow xenotransplantation have been reported, ambiguity remains as to their long term effectiveness. In this review, we would like to reconsider the immuno-isolative effectiveness of membranes reported from the standpoint of permeability and present our strategy to prepare membranes that can realize long-term functioning of xenograft. There are distinct different types of semi-permeable membranes, hydrogel membranes and ultrafiltration membranes. Studies on their permeability indicated that neither of these membranes effectively fractionate solutes on the basis of molecular size under a diffusion-controlled process, nor thus can they immuno-isolate xenograft for a long time. Humoral immunity including antibodies and complement proteins is suspected of playing a major role in the rejection of xenografts. Control of complement cytolytic activities, not antibody permeation, may be a key factor determining the fate of the xenograft enclosed in membranes. We found that the microbead containing poly(styrene sulfonic acid) can consume complement cytolytic activities and thus can effectively protect xenogeneic islets of Langerhans in diabetic mice from the humoral immunity.