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 post-mitotic 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 dopamine-secreting
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.(ABSTRACT
TRUNCATED AT 250 WORDS)
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