Article,
Immunocompatibility and biocompatibility of cell delivery systems.
Adv Drug Deliv Rev, 42 (1-2): 65-80 (2000)
Abstract
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.
Tags
- &
- *cell
- *drug
- ;
- adhesion
- animals
- biocompatible
- cell
- cytokines/administration
- delivery
- dosage/pharmacokinetics
- gov't
- humans
- materials
- non-u.s.
- research
- separation
- support,
- systems
- transplantation
