Encapsulated dopamine-secreting cells transplanted into the brain: A possible therapy for Parkinson's disease

Encapsulation of neurosecretory cells within a semipermeable membrane may possibly isolate the enclosed cells from the host immune system and allow inward diffusion of nutrients and outward diffusion of neurotransmitters. Moreover, the encapsulation procedure may prevent the tumor formation of enclosed cells, when they are derived from tumor cells. In the present study, PC12 cells, a dopaminergic cell line derived from a rat pheochromocytoma, were enclosed within in agarose/poly (styrene sulfonic acid) (agarose/PSSa) mixture and transplanted into the brains of rats (allogeneic transplantation) or guinea pigs (xenogeneic transplantation). Tyrosine hydroxylase (TH) immunoreactive PC12 cells within the microcapsules were observed in all rats and guinea pigs at least up to five weeks after transplantation. PC12 cells were round in shape and of relatively uniform small size. Although PC12 cells occasionally formed cell clusters, the formation of a tumor was not observed. The host reaction to agarose/PSSa microcapsules was minimum. The degree of glial fibrillary acidic protein (GFAP) positive astrocyte density around the microcapsules was similar to that around injection marks. There was no apparent immunological rejection around the capsules. High-performance liquid chromatography with electrochemical detection (HPLC-EC) showed basal and potassium-evoked release of dopamine from the PC12 cell-enclosed microcapsules in vitro. Although our data is preliminary, we believe that agarose/PSSa microcapsules are promising for producing semipermeable membranes that enable allo-and xenotransplantation of neurosecretory cells into the brain in the absence of systems immunosuppression. This approach is expected to be applied in Parkinson's disease in the near future.