Immunocompatibility and biocompatibility of cell delivery systems

Immunoisolation therapy overcomes important disadvantages of implanting fre e cells. By mechanically blocking immune attacks, synthetic membranes aroun d grafted cells should obviate the need for immunosuppression. The membrane used for encapsulation must be biocompatible and immunocompatible to the r ecipient and also to the encapsulated graft. The ability of the host to acc ept the implanted graft depends not only on the material used for encapsula tion, but also on the defense reaction of the recipient, which is very indi vidual. Such a reaction usually starts as absorption of cell-adhesive prote ins, immunoglobulins, complement components, growth factors and some other proteins on the surface of the device. The absorption of proteins is diffic ult to avoid, but the amount and specificity of absorbed proteins can be co ntrolled to some extent by selection and modification of the device materia l. If the adsorption of proteins to the surface of the implanted material i s 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 influenc ed by the device content. Xenografts trigger a more vigorous inflammatory r eaction than allografts, most probably due to the release of antigenic prod ucts from encapsulated deteriorated and dying cells which diffuse through t he membrane and activate adhering immune cells. There is an evident effect of autoimmune status on the fate of the encapsulated graft. While encapsula ted xenogeneic islets readily reverse streptozotocin-induced diabetes in mi ce, the same xenografts are short-functioning in NOD autoimmune diabetes-pr one mice. Autoantibodies, to which most devices are impermeable, are not in volved. Among the cytotoxic factors which are responsible for the limited s urvival of the encapsulated graft the most important are cytokines and perh aps some other low-molecular-weight factors released by activated macrophag es at the surface of the encapsulating membrane. (C) 2000 Elsevier Science B.V. All rights reserved.