Immunocompatibility and biocompatibility of cell delivery systems.

Immunoisolation therapy overcomes important disadvantages of implanting free cells. By mechanically blocking immune attacks, synthetic membranes around grafted cells should obviate the need for immunosuppression. The membrane used for encapsulation must be biocompatible and immunocompatible to the recipient and also to the encapsulated graft. The ability of the host to accept the implanted graft depends not only on the material used for encapsulation, but also on the defense reaction of the recipient, which is very individual. Such a reaction usually starts as absorption of cell-adhesive proteins, immunoglobulins, complement components, growth factors and some other proteins on the surface of the device. The absorption of proteins is difficult to avoid, but the amount and specificity of absorbed proteins can be controlled to some extent by selection and modification of the device material. If the adsorption of proteins to the surface of the implanted material is reduced, the overgrowth of the device with fibroblast-like and macrophage-like cells is also reduced. Cell adhesion at the surface of the implanted device is, in addition to the selected polymeric material, greatly influenced by the device content. Xenografts trigger a more vigorous inflammatory reaction than allografts, most probably due to the release of antigenic products from encapsulated deteriorated and dying cells which diffuse through the membrane and activate adhering immune cells. There is an evident effect of autoimmune status on the fate of the encapsulated graft. While encapsulated xenogeneic islets readily reverse streptozotocin-induced diabetes in mice, the same xenografts are short-functioning in NOD autoimmune diabetes-prone mice. Autoantibodies, to which most devices are impermeable, are not involved. Among the cytotoxic factors which are responsible for the limited survival of the encapsulated graft the most important are cytokines and perhaps some other low-molecular-weight factors released by activated macrophages at the surface of the encapsulating membrane.