Transplantation of Polymer Encapsulated Neurotransmitter Secreting Cells: Effect of the Encapsulation Technique

Abstract

Deficits associated with neurological diseases may be improved by the transplantation within the brain lesioned target structure of polymer encapsulated cells releasing the missing neurotransmitter. Surrounding cells with a permselective membrane of appropriate molecular weight cut-off allows inward diffusion of nutrients and outward diffusion of neurotransmitters, but prevents immunoglobulins or immune cells from reaching the transplant. This technique therefore allows transplantation of postmitotic cells across species. It also permits neural grafting of transformed cell lines since the polymer capsule prevents the formation of tumors by physically sequestering the transplanted tissue. In the present study, we compared the ability of dopaminesecreting cells, encapsulated by 2 different methods, to reverse experimental Parkinson’s disease, a neurodegenerative disease characterized by motor disturbances due to a lack of dopamine within the striatum following degeneration of the dopaminergic nigro-striatal pathway. PC12 cells were loaded in polyelectrolyte-based microcapsules or thermoplastic-based macrocapsules and maintained in vitro or transplanted in a rat experimental Parkinson model for 4 weeks. Chemically-induced depolarization increased the in vitro release of dopamine from macrocapsules over time, while no increase in release was observed from microcapsules. Encapsulated PC12 cells were able to reduce lesion-induced rotational asymmetry in rats for at least 4 weeks, regardless of the encapsulation technique used. With both encapsulation methods, PC12 cell viability was greater in vivo than in vitro which suggests that the striatum releases trophic factors for PC12 cells. More brain tissue damage was observed with microcapsules than macrocapsules, possibly the result of the difficulty of manipulating the more fragile microcapsules. Material resembling alginate was observed in the brain parenchyma surrounding the microcapsules, whereas no structural changes were observed with poly (acrylonitrile vinyl chloride) based capsules 4 weeks post-implantation. This fact raises questions about the in vivo stability of polyelectrolyte-based capsules implanted in the nervous system. We conclude that the implantation of polymer-encapsulated cells may provide a means for long-term delivery of neurotransmitters providing adequate encapsulation technology.