Lisa Christenson

A novel approach to neural transplantation in Parkinson's disease: Use of polymer-encapsulated cell therapy

Transplantation of dopaminergic neurons derived from fetal or adrenal tissue into the striatum is a potentially useful treatment for Parkinsons disease (PD). Although initially promising, recent clinical studies using adrenal autografts have demonstrated limited efficacy. The use of human fetal cells, despite promising preliminary results, is complicated by tissue availability and ethical concerns. An attractive alternative is based on encapsulating dopamine-producing cells into polymer capsules prior to transplantation. Polymer capsules can be fabricated to surround the cells with a semi-permeable and immunoprotective barrier. The semi-permeable membrane allows nutrients to enter the capsule, so the encapsulated cells will survive and function, and dopamine and other low molecular weight constituents to diffuse out into the host tissue. Thus, the technique allows use of unmatched human tissue (allografts), or even animal tissue (xenografts) without immunosuppression of the recipient. Cell-loaded polymer capsules can also be retrieved if necessary or desired. The demonstration that striatal implants of encapsulated dopamine-producing cells promote behavioral recovery in rodent and primate models of PD further suggests that cellular encapsulation may be a useful strategy for ameliorating the behavioral consequences of PD.

Transplantation of Polymer Encapsulated Pc12 Cells: Use of Chitosan as an Immobilization Matrix

Polymer capsules were fabricated to encapsulate PC12 cells within a semipermeable and immunoprotective barrier. The inclusion of precipitated chitosan as an immobilization matrix within the polymer capsules increased the survival and physiological functioning of the PC12 cells. In an initial study, HPLC analysis revealed that the inclusion of a chitosan matrix resulted in an increased output of catecholamines from the encapsulated PC12 cells under both basal conditions, and following high potassium depolarization at 2 and 4 wk following encapsulation in vitro. Furthermore, implantation of cohort PC12 cell-loaded capsules into guinea pig striata revealed that chitosan enhanced PC 12 cell survival after 6 wk. A second study determined that 12 wk after implantation into guinea pig striatum, abundant tyrosine hydroxylase-positive PC12 cells were evenly distributed within capsules containing chitosan. The long-term biocompatibility of these implants was good as determined by the absence of inflammatory or immune cells, and minimal GFAP reactivity surrounding the implant site. In contrast, implantation of unencapsulated PC12 cells resulted in a marked host tissue reaction, and destruction of the implanted cells within 4 wk. It is concluded that the inclusion of precipitated chitosan as an immobilization matrix enhanced the viability of encapsulated PC12 cells, and that altering the internal milieu of polymeric capsules may represent an effective transplant strategy for ameliorating human diseases characterized by secretory cell dysfunction.