Immunoisolation of transplants by entrapment in F-19-labelled alginate gels: production, biocompatibility, stability, and long-term monitoring of functional integrity

Transplantation studies with immunoisolated foreign cells/tissues (encapsul ated in Ba2+-cross-linked alginate) show that several obligatory requiremen ts have to be met before this immunoisolation technique can be used for rou tine clinical trials. We present chemical procedures and technical developm ents which could address and solve the current problems and limitations of the microencapsulation technique. Large-scale production of highly purified (biocompatible) alginate is possible and this material does not evoke any foreign body reactions under implantation conditions. Atomic force microscopy (AFM) studies suggest that geometric inhomogeneitie s may lead to immunological reactivity of the crosslinked alginate. Materia l traces released from fibroblasts, macrophages and/or lymphocytes migratin g over surfaces can also be studied by AFM and may initiate the primary for eign body reactions. Long-term stability of the alginate beads can be improved by incorporating proteins or (medically approved) perfluorocarbons during the cross-linking process and by subsequent treatment with 6 mM sulphate. Long-term stability and local oxygen supply can be monitored in vivo using non-invasive F-19-n uclear magnetic resonance imaging (MRI) of perfluorocarbon-loaded alginate beads. These improvements and developments allow clinical trials with allogenic (a nd xenogenic) tissue by alginate immunoisolation.