TRANSPLANTATION OF POLYMER ENCAPSULATED PC12 CELLS - USE OF CHITOSAN AS AN IMMOBILIZATION MATRIX

Polymer capsules were fabricated to encapsulate PC12 cells within a se mipermeable and immunoprotective barrier. The inclusion of precipitate d chitosan as an immobilization matrix within the polymer capsules inc reased the survival and physiological functioning of the PC12 cells. I n an initial study, HPLC analysis revealed that the inclusion of a chi tosan matrix resulted in an increased output of catecholamines from th e encapsulated PC12 cells under both basal conditions, and following h igh potassium depolarization at 2 and 4 wk following encapsulation in vitro. Furthermore, implantation of cohort PC12 cell-loaded capsules i nto guinea pig striata revealed that chitosan enhanced PC12 cell survi val after 6 wk. A second study determined that 12 wk after implantatio n into guinea pig striatum, abundant tyrosine hydroxylase-positive PC1 2 cells were evenly distributed within capsules containing chitosan. T he long-term biocompatibility of these implants was good as determined by the absence of inflammatory or immune cells, and minimal GFAP reac tivity surrounding the implant site. In contrast, implantation of unen capsulated PC12 cells resulted in a marked host tissue reaction, and d estruction of the implanted cells within 4 wk. It is concluded that th e inclusion of precipitated chitosan as an immobilization matrix enhan ced the viability of encapsulated PC12 cells, and that altering the in ternal milieu of polymeric capsules may represent an effective transpl ant strategy for ameliorating human diseases characterized by secretor y cell dysfunction.